08:03:18 Alright, so welcome everybody to the second discussion on non equilibrium fluctuations of fluid membranes and solid shells.
08:03:26 Today's discussion will be chaired by Cecile Sykes, and I hope you already watch the two pre recorded talks by Patricia Bizarro and rich pastor.
08:03:35 So again, I just want to just remind everybody that you know like whenever you're not speaking, please mute yourself so that you know we can minimize the background noise, and also if you would like to get the word, please, you know, use the raise hand
08:03:50 function in zoom by going to the reactions. And then, just as a reminder, the discussion will be recorded and then like uploaded on the KTP website.
08:04:00 And then just another comment before we start, you had like very lively discussion on slack and you know we hope that this will continue. but it was just yet.
08:04:24 can be organized in threats. Because sometimes, you know like, people reply to you know like specific questions by writing a new comment here, but rather than doing these, it's actually better if you know if you want to reply to specific comment if you
08:04:34 go if you just, you know, go with your mouse here, and then just use these like reply in threat option and then this will like reply to the specific question because then everything can be nicely organized.
08:04:46 For example, if I look at these posts from Petya it already has 14 replies, and then like everything is nicely organized in one place, and one doesn't have to you know scroll up and down the, the, the whole slack to see how things are organized so this
08:04:59 is just like a minor comment of how the you know how maybe we can improve the organization of sex but otherwise, we are super very happy that you know you guys are actively participating on slack and hope that this will continue.
08:05:14 So with this, you know, let me stop the remarks and then I'll give the floor back to our CEO psych school moderate the discussion today.
08:05:25 Thank you.
08:05:27 I'm so thank you very much to the both speakers for their great talk.
08:05:34 I think you're both the winners in length of talk so I hope you will remain.
08:05:42 Um, and so I think Patricia still was very interesting, because it has a great historical perspective and Richards talk was very invigorating for simulating monitor years inviting us and the complexity with part two.
08:06:03 Right, so I suggest. I'll start with the questions, I will start with the questions to Richard on to Richard, and then to Patricia on the slack thread.
08:06:16 I mean I'm on the slack conversation so I will take a few questions there, and then open to the floor, and we'll see if we, I mean if we need to do otherwise.
08:06:30 And so I want to start with Richards, continue but I guess. Okay.
08:06:37 In fact, questions raised by Carlos So Carlos Marcus, the other one.
08:06:44 And so one question was about the origin of filament is of the filament is nature of your clusters.
08:06:51 So you already partially answer to this question but can you elaborate on how you can you can explain why you have these filaments and structures positively to like domains, more circular to domains.
08:07:13 But
08:07:18 we're still working on it. But just in case people didn't read the read my slap response so the first thing that Terry Denson told us when, when you started analyzing these clusters.
08:07:31 Is it.
08:07:32 It's like a mineral, so actually looked at milestone phosphate calcium mean minerals, and they don't look like that at all.
08:07:44 Mineral is 3d and it's actually a rock right.
08:07:48 So, but what we find when we look at the radio.
08:07:54 The distribution functions of the various accidents on the bus page with calcium phosphate has a
08:08:07 three oxygens one's a double bond and you know half of the ones on the ring or singly charge so just one of the phosphate charts, the other, the other, you know, once the webinar, itself, pit.
08:08:25 At the P for the P five. So, one of those is always doubly charged. And then the other one is always singly charged. So, you have numerous ways that every bit can interact with with like calcium and then form a link with with
08:08:51 another pack. So if you just think of, of a pip to ring having, you know, two phosphates So, one can link with a guy on one side and
08:09:03 the other one on the other side plainly that's, that's like not what's happening. I realized I'm not answering your question. Why don't they form a single type cluster, as opposed to a string.
08:09:18 I'm just explaining that it's not like a Lego set where you can just like snap them in and then easily get a ring and easily get a straight one, it's, it's numerous
08:09:35 the atoms, doing different things, including the one phosphate.
08:09:43 So, at this point I'm just, you know, observing that in the model as they form these long strings, not little pipe clusters in.
08:09:55 In the violators they formed short strings.
08:09:59 And you know it's it's it's a question that's making us think more about this. I'm like preface my part of the clock. I like had a dream last night that I was still in graduate school.
08:10:17 And like woke up and I was like really happy that it's been like, you know, 40 years since I've gotten my PhD.
08:10:25 And then I realized, oh it's this meeting that's making me feel this way.
08:10:32 Like a thesis oral, but anyway.
08:10:37 The question was, how these questions are are sensitive to expansion, so how remain under expansion. If the answer
08:10:55 is not so much. So, we did that, I gave the deal I.
08:11:03 The model layer paper, and in the model layer paper.
08:11:09 We like simulated at three different applied surface tensions. So the model layer is basically pulled, and it hardly changed things. And you know, if you think about it, it's maybe not too surprising because it's not a crystal, like you know you shatter
08:11:29 it it's it's sort of this film at this you know snake like string you extend it slightly that will snake just, you know, extends itself. So the answer is, it's like not very sensitive to surface changes.
08:11:48 Okay. So another question by Rumi about the curvature. So, I mean, She. She first addressed, whether we could think of the molecular curvature but then you say, No, it's too dangerous.
08:12:04 So let's look at
08:12:07 within the cluster or the curvature of the scale that is higher than the one over limpid. So could you link your simulations with curvature of the membrane local curvature.
08:12:32 Do you see you see the membrane curving under pressure. Oh, no. I mean, well I mean, there's there's, there's two kinds of curvature, one is actually curvature where the membrane will will will just band.
08:12:44 We don't see that. Now, the other one is, is the spontaneous curvature, and in fact I was expecting that when we, when we calculate
08:12:59 the, the pressure to answers, we would see some evidence of like spontaneous curvature formation. Now as a lot of the theoreticians now to calculate a spontaneous curvature from the violator simulation.
08:13:20 It's this first moment of the pressure to answer. And then that equals to the spontaneous curvature, times the bending constant, there's no easy way presently to calculate bending constant of a multi component, all Adam by layer that's, that's because
08:13:40 the by layers like too small to calculate bending constant using the height fluctuations, you like need about 8000 leopards about about 20 nanometers, which is much larger than, then, then like we have.
08:13:59 So getting back to my problem with the oil nm simulations.
08:14:03 I haven't been able to extract a
08:14:09 spontaneous garbage, or, or, you know, sort of a clearly obvious change in that first moment of pressure dancer. So I conclude at this moment, that, that the aggregation of like this, leading to a very small, as much as curvature change.
08:14:32 Okay, maybe last question before we go to Patricia from Amoeba, which is related to this one.
08:14:41 About the clustering of specifically pigs would be interpreted in terms of a coarse grain foods field.
08:14:57 So, can you, can you give your thoughts about that. Sure, I mean I think they're like big thought is to really look at the largest clustering of like out of
08:15:13 protein
08:15:16 paper to wrap, we, we will, you know, need to go to up to a coarse grained level because he the oil item simulation just can't get get to that lens scale.
08:15:32 As far as the, the details of
08:15:40 the martini modeling.
08:15:42 I mean giving the kind of
08:15:46 film method structures that we that we observed in the, in the old Adam simulation.
08:16:11 So one of the things I'd like to say either working with someone or someone doing it immerse yourself is to actually work out a martini model that can generate the kinds of clusters that we see.
08:16:25 And then, when we got off. The other thing I want to say as far as the martini model, and even our simulations, we're all doing this with a non polarized about force field.
08:16:40 It's not likely that when we do a polarized force field, which we're working on for a new one will get some
08:16:52 some some differences. So, these are just the details that the simulators, you know, that need to live with.
08:17:03 But, yes, yes Martini.
08:17:07 Go ahead and try. Good luck. Let's do it.
08:17:11 Right, Thank you very much.
08:17:17 No, I'm. Oh, I'm Pastor questions to Patricia.
08:17:20 And so at the beginning of this conversation there was a great deal about this effective temperature. So Mark is in the back of the envelope calculation and he found that the effective temperature is very high in fact hard to explain how where this energy
08:17:39 goes where it's come from, it comes from, and what could we do experimentally, I'm in.
08:17:50 With, I mean, what could we do with this effective temperatures, it's a mathematical definition of temperature, everybody understood but what, what can we do further with that.
08:18:03 Yeah, so, so there was a question about it was Marcus also question, a question about why we should make a kind of simple, simple estimation about how much you heat the system.
08:18:16 So basically you expect that the temperature will be like a Michael Calvin, Calvin or something like that. Right. And so I think that probably my answer to that would be that a new editor, the energy, the energy which is related to this protein pumping
08:18:32 in our case is not dissipated in the water in them directly at least by heat but is mechanically dissipated. And it could be because of protein is directly mechanically anchored in the in the membrane.
08:18:45 It could be also dissipated in the dark because you could also have some I don't do any flow going on, but clearly the, this, this.
08:18:54 So basically the, the energy, eventually dissipate and much more, much more efficient way I would say, to be detected by by our experiments.
08:19:06 And I would say so the question about effective temperature so, so, so, how to start with that. I would say, considering the experiment which have been done, well done in the past.
08:19:19 It was, in fact, the easiest interpretation of our data, because what we were measuring originally was kind of cramping of the membrane. and we didn't have any access to.
08:19:31 In this case to to the creation spectrum of the of the of the monitoring.
08:19:48 I would say that if if the, If the flickering spectroscopy is developing better. And maybe we could, we could hope to be to do better than measuring and effective temperature.
08:19:59 Maybe musically we could hope that we could measure really deep down, I mean, the change a different situation spectrum, as compared to a to a festival on brain right.
08:20:09 So, I don't know if I answer the question is so basically, the number one.
08:20:13 That's right. Thank you. So another question that was related to that is, what about defining an effective tension, because in your attention as a lot
08:20:27 of attention as a function of temperature, you see that the active ones are lower than the objective points are lower than the massive points, then you could define instead of defining this temperature you could define an effective tension.
08:20:44 So, and there were questions about this on slack so if you imagine that the effective tension decreases. So, I would think of an example of the entrepreneur spring I've done that to mainstream in front of my students a few times, I mean you can really
08:21:00 take a rubber, eat it with a, with an hair dry hair dryer, and then it will shrink. So could you imagine an experiment where you would measure that this tension decreases.
08:21:18 Sickness what we what we did and in fact we were married with flickering spectroscopy we're measuring a change and effective tension which was reduced, when we had the reactivity of the protein so it's exactly what we were doing by flickering spectroscopy.
08:21:29 So seeing that it's it's it's a really what what what what you what you see the first effect procedure for measure featuring spectroscopy is really, and as been seen by different groups when they were measuring filtration spectrums you really see that
08:21:45 the tension or the SS the low mode amplitude was increased so basically this is a direct evidence that the tension at least an effective tension is a is a reduced in terms of when there is activity.
08:21:59 Because you have more frequent more greater amplitude of fluctuations, but how, how would you measure it with a, with an operative Can you can you imagine an experiment where you see the tension that you when you pull in a membrane detention decreases,
08:22:14 it may or may not be possible.
08:22:17 I don't know because it's always there are there is always enough a question about how you measure attention so I think that it's, it's not so he's a nice to another question but I don't know.
08:22:28 Yeah, i mean the problem is, there are not so many ways either you control attention and to measure it. I don't think, besides measuring flickering.
08:22:37 I think there is not much, no not no other method which could allow for the moment to measure effective tension maybe in the audience somebody ever. They may be the only issue you have a better idea that but I don't know necessarily I don't, I don't see
08:22:53 better ways to measure an effective tension without interfering with a with a with a system
08:23:02 me on this, or pulling tubes is one way of measuring. I mean, put tubes and measuring just the thickness of them without holding them with a with a pipe it without limits you without holding the paper with or without owning the visitor, this is Stefan.
08:23:22 So I think this is very yes I seen this way I mean without interfering with, with a membrane senior I'm not so many techniques. And if you think about maybe the dyes that measure I think he wouldn't he wouldn't, maybe it's not a good reporter about this
08:23:38 kind of, let's say, active to the property, you know, die, which would be on which report and based on these are for instance, for instance, we report about the stretching mongering so I've seen is probably not the right range of attention, it could be
08:23:54 accessible with with with this kind of experiment. So I would say so far.
08:24:00 My opinion there is no major way to measure this this then measuring the figuring on patient.
08:24:09 Okay.
08:24:09 So just a, the dice that you mentioned, Patricia have already gone through this tension sensitive died flipper flipper I think, yeah, I think it would not be sensitive in this tension range.
08:24:22 Exactly, exactly. So say it is really good for high tension but he is getting low tension so I think that.
08:24:30 Yeah.
08:24:32 There was, I mean we at least there was one way we did it, but in a different way so it was experiments which were done by fusing at high rate of physical with a giant physical so you could easily detect instability so you could really follow instability
08:24:47 growing but this again. The way this case to measure I mean, you can detect because you get to my fusion you decrease, gradually his attention in anonymously runway.
08:24:58 You also get instabilities but again it's by measuring on pit unification in a sense.
08:25:04 Thank you so I see the floor is warming warming up So David, you are the first question question David Nelson. Sure. So thank you, Patricia It was really a beautiful summary and nice to be reminded of the old work by by Robin and jock, which I think might
08:25:24 have started over volleyball game on the beach.
08:25:31 It was it was nice because he started at KTP so,
08:25:36 so, so I like to get a better intuition, if you could about the difference between channels and pumps. When you say channel I think I understand what a pump is and it pumps, and things sort of the wrong way and goes up a constant creation gradient, the
08:25:53 channels you're thinking of as being driving active membranes are they open and close but they don't actively transport and are those.
08:26:06 Also, what's the difference.
08:26:07 Theoretically and experimentally.
08:26:11 So, technically I'm experimentally so you can think about the channel as a whole, which is closed in some condition, and when it's opening.
08:26:21 So you have like a gate open you can imagine that this, then you have the four ions and the is they go along the gradient right yes okay in the palm that go against it right and, but basically what you can imagine that you have a permeation, what you
08:26:35 have is like an active formation of the moment. So you have a flow of ions which depend, which is dependent on some source of energy which could be could be stretching it could be a teepee could be something again.
08:26:48 So, the difference in this case is, you have this the flow from the primary permeation which, which is activated in a path, this is different.
08:27:00 By definition is again is going against the gradient, and the number of irons is very low. So basically this permission effect is is small. But to do that, the protein, as usually to do some mechanical confirmation will change so basically you have to,
08:27:16 to open a small let's say a small cavity and just open just away so there is a lot of mechanics associated to pumps, and this can eventually lead to some mechanical distortion of the membrane, for instance, he can use the protein is also able to switch
08:27:35 to switch confirmation with a large external part, but then you could also create some dynamic flow.
08:27:44 If the protein is rotating is also can run it can induce also some rotation in the membrane. You can also induce as well. Some rotation in the freezer around.
08:27:54 So as in, then I would say, you can say on the, on the night on scene in 20 intuitive part, how they can be different.
08:28:04 So and and i would say, on the theoretical part so basically said, they are not be having the same way.
08:28:13 Because.
08:28:16 So how can can I say that properly.
08:28:26 In principle, so the fact that pumps in principle, should they should that so the force, I mean, basically, if you consider the full system with the pumps you expect that zero force should be applied to to the to the market I mean basically the system
08:28:29 So, the difference is spectrum and for a space these pumps versus channels.
08:28:41 should have no external force. So for the pump.
08:28:46 You expect that the only, only term which should appear on the spectrum should come from the first moment of the force and not from the force directly.
08:28:55 Maybe I'm not answering your question. No, no, no, that that's that's very helpful. And one last quick thing. What if you can people added slip basis and enzymes at the flip the flip from one side to the other and will that make a membrane, have some
08:29:18 in some things yeah singing would be awesome. Yeah, I think is a different maybe Class of. Maybe, maybe you have a full day but in this case maybe it's not in the same class but the thing you will do exactly the same thing, it will it will, it will create
08:29:25 some distortion in the manner in which depend on the source of activity so I don't know if in this case it will be a bipolar I will be a dipole will be appropriate, but I have no idea this i i don't know i leave that to the tradition but for sure it will
08:29:39 be, if the if the system is activity has to be active, you will be also that I mean we also will create like a moment.
08:29:48 Thank you. Thank you very much to see my friend Reinhart the power ski on the, on. So, I was going to ask is, is somebody raising his arm, wanting to ask a question related to the subject or
08:30:03 no okay so rain hot, you're hot, you're the next one.
08:30:09 No Why not.
08:30:13 Turn your mic on. I don't hear you.
08:30:18 Hello. You hear me.
08:30:20 Yes.
08:30:22 I'm interesting talk.
08:30:24 I just wanted to start with. What you said was in your talk, but also now in in some responses about the difficulty to actually measure the flickering spectrum is a case of pumps.
08:30:38 Because I, as far as I understood what you did with you effective temperature, I mean you.
08:30:46 You have a ratio of copper divided by T or T by Kabbalah, and you'll find out that the temperature, effective temperature is about effective to increased right.
08:31:04 Well, I could also say that rigidity is decreased by a factor of two.
08:31:10 Yes. Yeah, so basically your wouldn't wouldn't you expect them, that actually your fluctuations in the microscope would really change quite a bit. If you, if you have to factor of tunes effective temperature.
08:31:27 Why don't you see me it seems to me. I don't know this is not what you have said but it seems to me that you that you had problems to actually see the effect of the pumps on the flickering spectrum now we saw we see big effects.
08:31:41 In fact, we had a big effect on the 10. So, I mean, the problem so we did two types of experiment was one was with with michael bay bay desperation. And in this case, you fix attention with the aspiration and what you measure is basically you imagine
08:31:56 it and the access area. And then in this case we could as well we could we interpret our data with an effective temperature, but in practice, you could as well.
08:32:06 I've interpreted interpreted the data with bending rigidity, which would be divided by two. But we were doing also experiments in with a flickering flickering spectroscopy, and recurrent spectroscopy you could really see that you have an enhancement of
08:32:22 the situation. And so in this case we didn't control the tension. So we saw an enhancement, or lo que which is which, which is really the sign that the effective tension is attention is decreased, and effective tension is is reduced compared to the case.
08:32:39 And if you look at the, let's say the high IQ then we could measure the, the effect of bending, I mean unbending rigidity and we recovered. I mean, in this case, but we were finding on the on the on the list, considering using using the theoretical model,
08:32:56 we were able to also fit our data I take you with with with in this case not a reduction of the bending rigidity but, including this dipole moment that we were measuring.
08:33:10 It was our bypass experiments. I was referring to in one slide you had this sort of looking at my to prepare escalation experiment and you did use this effective temperature.
08:33:26 Yes, which was about twice as large as, as in determined PS.
08:33:33 Know what I'm talking about is some kind of consistency shake if you know look at the flickering of the physical, wouldn't you expect to also see this enhanced temperature in quotes in the frequency spectrum.
08:33:47 Yes.
08:33:48 And you said I didn't get it didn't use, you are listening. You saw effect or have to also.
08:33:57 Let me find the slides, maybe we'll be back and show slide.
08:34:02 Yes.
08:34:07 Maybe the slide is here.
08:34:09 Okay. If I try to share my screen
08:34:19 screen.
08:34:21 Maybe this one.
08:34:28 You see something many slides now. Yeah, yeah sorry for that this this one is not the right one. This one should be the one thing. Yes.
08:34:39 So, basically you are talking about this from it.
08:34:43 So basically here when we have is a filtration spectrum, that's emerging read this is the best human brain and in green the adaptive one, and you could see that as high as a small few so here we have a very, very strong difference between the two.
08:35:01 The two care but you see also that IQ. We also see a difference.
08:35:06 So the difference exists at look you and IQ as well so we can see a difference in all the spectrum.
08:35:16 You know, I, I was referring to what you were one of your previous slides, where you had this, so I mean if you can't you get an effect, let me say it like this contract get an effective temperature out of the system.
08:35:30 So in this so in the first one is the one with a pet. Right, right. It is on this was this one he was with Michael Bay Packers curation. Yeah.
08:35:43 And I agree with you so in michael bay bay desperation so what you measure this is regarding the terrorism of the tension. This is the access area and the slope, as you say, is the ratio between the bending bending rigidity and attention and in temperature,
08:35:59 right. In this case, we have interpreted this data was an effective temperature so in this case is consumer GPS but this is, this is exactly the same experiment with better adoption.
08:36:11 So this is what we were in right yeah but did you see just to make this point that you could also think of reducing the rigidity right.
08:36:21 Okay, this law because, because if you think in terms of molecule confirmations what you really have, I have confirmation changes on the, on the level of a signal so to speak.
08:36:36 And I think this is, you know, this is defects like curvature defects in the membrane, in particular because these
08:36:47 molecules are these pumps are not symmetric, I mean they have a certain orientation it's random as he as he told me in the chat but if I look locally.
08:36:56 Each member important has a certain orientation.
08:37:00 And now you have some kind of a confirmation change which means you have sort of some kind of local changing of the memory structure.
08:37:10 And this is a bit like a, like a curvature defect isn't.
08:37:15 I agree with you. So in principle liquid, I mean you could think from from this kind of experiment you cannot conclude and I agree with you, you could imagine that luckily you have an effective.
08:37:24 Let's say that the rigidity is is a is a word his, you have a spontaneous curvature which is changing his activity.
08:37:34 And then, the capacity, the bending rigidity is changing because of because of that right. So I think from this pipe at experiment, it's not possible to, to conclude on that, because what we measure is there is just a slope of this tension vessels it
08:37:48 so we conclude. And then, I guess, I guess, i guess to the spectrum if you have known spectrum.
08:37:56 we conclude. And then, I guess, I guess, I guess to the spectrum if you have known spectrum. As far as I could see this is not the same party in the same pump, but it is.
08:38:02 Yeah, we did. We did the same thing with vector obscene was a bypass so we is where we found this affected to get one wasn't practice three that one affected too but if you analyze the spectrum you it was a good effect to have yet the same kind of effective
08:38:16 temperature as intended to this kind of inspiration experiment. Yeah, so if you go if you go now like hi QIQ so basically we find that we find a contribution which is compatible with that, we get we get something which is compatible with that.
08:38:35 But I would say maybe this model doesn't allow to to distinguish between, let's say, a modern where you would have, let's say, an effect on the on the effect of the change of information directly on this, on the bending rigidity, or.
08:38:52 I think we probably we cannot distinguish maybe we need. we need maybe as I would say maybe, maybe, we have to test them are dealt with. I mean with maybe other trick I would say maybe by changing.
08:39:08 I don't know, maybe the composition of the moment I don't know, but at least from that based on these experiments, maybe not possible to distinguish, I would say.
08:39:17 So there are many other questions coming in, increasing. So, thank you.
08:39:22 So the next one on my screen is a marrow shall do I pronounce okay.
08:39:31 If you can put down your your your your hands, that would be I want to thank you.
08:39:38 Yeah, so I did.
08:39:39 Yeah, my question is, so in one of your last slides you talk about these ATP synthesis of rotary machines that Coster in the membrane upon activation.
08:39:54 So we know that also for this linear pumps and channels, our day can re Viale induce hydrophobic mismatch in the membrane.
08:40:02 Have you also observed each couldn't use attractive interaction between them, have you also observed the clustering of those linear pumps and channels in the membrane and inducing different domains with different rigidity and versus dynamic fluctuations.
08:40:23 I said beautiful question so it's a. In fact, I have to say to tell you that the experiments I was describing we did them.
08:40:29 10 years ago more than that. So at the time we were not very much equipped to look at.
08:40:35 Let's say, maybe, maybe protein clustering or so i think i would i would love to do that but as a scene we were not, we didn't do it. And I would say there was no evidence so it doesn't mean it doesn't it's not it's not existing but there was no evidence,
08:40:51 because we are not equipped to look at it. So, In principle, you would expect that
08:40:58 if you have protein which somehow, I will say distorts enough the mother the membrane, you would you'd expect or so it's not some put some protein, modern modern media to the protein.
08:41:24 But I would say this is something I try to explore right now with another type of transporter, which is, which has a V shape and exchanging information in a very strong with a strong amplitude.
08:41:28 So, but at the moment I don't have the answer but in principle is expected for many proteins right, not only the rotating one.
08:41:37 Okay, thank you.
08:41:39 Marcus.
08:41:43 Thank you. I have another question for Patricia but actually be willing to just yield and wait for a little bit to answer questions for Richard, I mean I don't know how we move about this, chill out chill I asked for sure we do another round.
08:41:57 Well, good. Okay, so I go ahead. It might be related to what we're talking about I'm basically have a confusion about the minus sign here about what the tension should go up or go down in these experiments, which is, since since I can, if I applied engine,
08:42:14 I remove fluctuations so conversely if I see a membrane where suddenly the fluctuations go up, it seems natural to assume that the tension went down.
08:42:23 On the other hand, if what I have is a system where some internal machines are now starting to jiggle the membrane a lot more. The empty increased empty to do these fluctuations requires more area to accommodate them.
08:42:36 And so I would rather expect under these conditions the tension to go up but you would like to have more membrane in order to get so that confuses me, can you help me out with thinking about this that had exactly the same problem.
08:42:49 So, for me.
08:42:51 So you're right because we have a finite, so you could imagine if it would be true. If you have an infinite system, but now since the membrane is a there is a finite volume and a finite number of limited, choose expect that.
08:43:05 Now if you start to trigger more at some point the, the fact that we have a finite system should show up and now I don't have a good, good, good answer to that so maybe I mean it's something which caused me a lot.
08:43:18 I know that Lamont in
08:43:24 Denmark was a, was it was thinking about that but i don't i mean i don't have a correct answer to why we have this kind of amplification of the situations, not only as there was other experiments I like Tim Albright or socially sharing the same stuff
08:43:41 but I don't have a good answer to that, just to make sure I understand how this experiment with so you have a bicycle and Cena micro pet and those will sort of model.
08:43:51 I know, in this case so when you measure the fluctuations, you have a pet.
08:43:55 Okay, I was referring to the, to the first one that you showed with the one with a pet you fixed attention so in this case, don't say there is a change of tension you fix attention, and you measure the success of real, which is which, which is, which
08:44:11 a case wouldn't be what it is right, so what you do, you have a crumbling membrane. And you, you forgive an aspiration you measure the, the, the, the area that you unscramble that would say so.
08:44:32 any effect on attention because you in the sense of if you have it under a given intention. And it's been a passive situation as a certain micrometer let's say in the tongue of the of the microphone. and you know, turn on the activity, and it starts to
08:44:42 fluctuate more, I would then imagine that the bicycle is pulled out into the into the, into the compartment and pulled out of the tongue, and that would suggest that the tension went up because the bicycle is now pulling harder.
08:44:56 That's what the iPad will tell you, and if you now say, if you do this without a pipe pet, what would be different. The tension should be going off.
08:45:05 But I think the tension is fixed in the microphone a desperation technique, it's fixed so if you change if the physical changes it, the pipe it will raise it to its value to it's given value you see, so it's completely fixed by the experimental system.
08:45:24 There's active feedback.
08:45:26 No, no.
08:45:30 I mean it's just, it's a level of water, so you fix a difference in the level of what you fixed it you fixed it.
08:45:37 You fixed fixed the aspiration for liberation right and and that gets fixed it can't, it can't change. No, no, what is the ones that what I'm saying is that there's might be a point one dimes per centimeter attention that comes from the aspiration.
08:45:51 And there's a there's a potential in the vessel and they have to balance in the Colombian.
08:45:56 And now you turn on lights flickering in the vessel. And if this increase the tension of vesco, then these two springs are no longer balanced and so membrane would be pulled out of the pipe, that's what I'm expecting, until they are again balance.
08:46:18 So that to me would be an indication that the tension that the flood that the antidote is population goes up as you can optically See, but it will also indicate but the tension goes up, which normally you wouldn't expect but you have an active process
08:46:30 from the equilibrium formula stone apply.
08:46:35 So what you say that there is one minus sign is incorrect in the interpreter.
08:46:40 I don't know I'm just saying. Under normal equilibrium conditions. there's obviously a relation between less tangible fluctuation.
08:46:48 You know I have a process that for what I just imagine just you're holding a rope between two people with some tension. Now somebody violently starts to wiggle the rope, you see more empty to try to the rope, but at the same time that will pull the rope
08:47:02 together. So, I'm saying understand any of this. I'm just saying I'm confused about that sign. Maybe you need to discuss later because I'm two more.
08:47:17 Hi. Thank you, Patricia for for the talk. I have some minor comments and several questions. The first one is all about this effective temperature, probably, it's a little bit misleading misleading words because what you have is external perturbation external
08:47:39 noise that was induced by by these active proteins. And what you see is that this noise is twice or is twice higher than the thermal fluctuations, and probably it misleads.
08:47:59 The term effect of temperature can mislead people to,
08:48:05 to think that something happened with temperature. Just a comment.
08:48:11 The other thing that how Aqua Sun is, they're very good analogy with the road that indeed if you have these external white noise, it should somehow increase the tension in the membrane.
08:48:32 Pretty fits.
08:48:32 And I think I had a small question, or just maybe we missed it on the presentation. What does means the first moment of the forest what forced to me.
08:48:44 What.
08:48:46 So then this moment or fourth force.
08:48:49 Yeah, so the thing the first in the first.
08:48:53 In the first move that which was proposed the force was related to Channel and Channel and as I explained before, basically he was donated to a kind of a local a permeation local promotion which was, you know, going on when the channel was on.
08:49:05 So this was, this kind of force on the moment which was which was considered right the fact that you have locally a flux of ions going through. And, but it's not completely white noise because basically this protein, they open because they have their
08:49:25 own shut noise. And in addition, they also diffusing the membrane. So, basically, there are, I mean there is some correlation at this in time in space, related to this diffusion, so it's not completely random indices.
08:49:40 I see another thing another tremendous concern Reinhardt's a question about that you cannot distinguish the i that is higher fluctuations due to affect temperature or it's bad liquidity.
08:49:57 I think that the first thing that the analogy that's made Malkmus is pretty distinguished situation, if you have the lower rigidity, you should you should test, but probably if you have lower rigidity, then it wouldn't lead to increased tension between
08:50:20 the between the people that hold their roots, but if you have the increased noise induced by channels, it would lead to the increased tension.
08:50:31 It could somehow distinguish between these two,
08:50:36 two situations. And another thing is, maybe you can try to measure it bandit projecting the static system like nanotubes So, something like that.
08:50:50 Yes, I mean yeah the time we didn't do it so I agree with you, we could measure the, let's say, a change on when you read about the agenda and venue rigidity with other techniques right.
08:51:02 Although, although I mean now if you have tubes and you have you have protein, changing information etc So then, maybe it's not so easy to interpret at the end of the day.
08:51:14 Yeah, yeah, so I assume they maybe this is not so subtle.
08:51:19 That, and to come back to what present the data point about.
08:51:26 So you had a comment about the, the analogy, everything is the rope analogy. Yeah.
08:51:37 So, so in this case, how do you explain that we have in the flickering spectrum and increase of the, of the amplitude and even very low qy the noise that is provided by the proteins do not explain these increase.
08:52:03 Doesn't it.
08:52:07 Don't know that it's not enough to worry too know. Okay, you go downtown and discuss that the three of you rain hot Timor and Patricia, and so we can move on with your questions, if you're right with that.
08:52:29 Thank you.
08:52:30 So, the next one is a man who was very active on slack Thank you very much. And before I asked his question I'd like girls to raise their hands, I have seen one that disappeared.
08:52:44 Please girls Raise your hands are getting in your number so it's your chance please do it, we will have the time of Ahmed, asking his question to prepare your question.
08:53:00 You may win a prize.
08:53:02 Oh, thank you, penny.
08:53:03 Good.
08:53:05 Good.
08:53:07 Oh, thank you so much. Patricia, for everything a lot of questions but I would just boil it down to questions for now. The first question is, for example, is have a process, and that changes the thickness of the membrane, and that changes affected in
08:53:22 spectrum. So what I regard that as a non equilibrium phenomena, or is it still an equilibrium phenomena.
08:53:28 So you are a theoretician right.
08:53:31 No, I'm a mho right so, do you know how to change the piece of the membrane dynamic and this asking the right.
08:53:45 Do something like that so something or something which is basically tinting or. So I think in particular, if it's, I would say if. Usually if it's greater as energy.
08:53:54 So to change the, then I would say for me would be a exactly in this, we will create some, some, you will completely being discussed of a phenomenon that discusses now for almost an hour.
08:54:10 I think it'll be fine. I mean, any anything which is active and and i mean affecting, even if it's affecting the signals would be fun.
08:54:20 The other question I wanted to ask before you went over beautiful history of how the activity was kind of pro human future when you're doing fluctuation analysis we can look at the data from different perspectives.
08:54:34 For example, you can look at the fluctuation spectrum, you can look at the time correlations, you can look at the detail balance, and then come up with a final conclusion based on all of this data, or you can just look at one part and just.
08:54:47 So what I see and what I've seen is that only one part was kind of probe like for example in the DNS papers people just look at time correlations, but then they never talked about I think the the fluctuation spectrum or they've never looked into Peter
08:55:03 balance for example but that came as a later technique I guess, so in future this may be like a good conclusion that step to look at all different perspectives and then come with a final conclusion.
08:55:16 I fully agree with you i mean basically what happened is probably. We are all experimental This is a setup and then basically we have a, you know, we have developed some analysis that we didn't develop all the range of analysis.
08:55:28 So I think maybe we should maybe team up in some cases to kind of, you know, decide about the system and use the same system and compare what we get, with different approaches.
08:55:39 So I think that you could you could realize that, you know, my, My, my review was not extensive But still, there is a much more theory existing right now, maybe not enough and and, but clearly not enough experiments so for sure there is a there is a need
08:55:58 for, you know, as you say, having more a more complete more comprehensive description, a different scale different timescale of space care etc. So for sure there are different things to be done.
08:56:13 I completely agree with you that.
08:56:24 And I worked on it. Yeah, and we've got back from that. The one that will destroy to embark on what is the crossover model where there because there isn't.
08:56:29 There's a tension between and then the vending machine right but we don't know what is the crossover more that goes from the tension between to the vending machine.
08:56:37 So maybe that would answer the question whether we are seeing the changes in the bending rigidity or changes in the effective pendulum.
08:56:55 I would say, the way we were at least fitting our data was was with with this kind of dipole model which can include a diaper energy and. So, basically not getting no effect on those on the, on the venue rigidity and some, some changes in the ineffective
08:57:04 ineffective tension, right. So I think we were fitting this data with with this model, but, I mean, it is this model, the only one we could fit that in basically to know if the model is correct, you have to change even more parameters so I think that
08:57:18 kind of effect, then it would be even better to me there is more data from different groups, maybe we have a chance to to really probe the different model and see what is working and not working, but for the moment I would say that that are still scars.
08:57:52 Now, thank you so much. Thank you so afraid or would you allow me to give voice to bed mini first. Okay, so for me.
08:58:01 I feel so special. Thank you. Yeah, I was trying to organize my thoughts I'm so basically Patricia.
08:58:08 Patricia thank you for the talk, I actually wanted to follow up on something Reinhard mentioned, my questions in the chat, basically thinking about the multi scale effects right so if you have a or protein in the membrane that has undergoing active confirmation
08:58:26 changes, then you can imagine that there are thickness changes, potentially tilt changes and interaction with the water, the whole. So how
08:58:37 can we even think about it and I sort of want to go back to some of the work that john box for me I had done, thinking about the destruction, if I remember correctly here I can see him on my screen is here, I was hoping he would
08:58:56 forgive me for potentially butchering my recollection of beautiful work.
08:59:02 So you, you have changes in the thickness of the violator but also there's the potential this tension so the length scale over which that could relax and then the tilt.
08:59:15 And those could be of the same order of magnitude I say the curvature changes if you look at the link because I'm trying to work this out, and I didn't manage to finish the analysis I was trying to do after I heard your talk so I just have a bunch of
08:59:32 half the equation so at this point. And I was just wondering, in terms of experimental measurements right so we can write some of the theory with maybe tilde or distinction in terms of experiment on measurements, what could be done.
08:59:52 So, not too much. So what could be done means that to to question your what could be done one is to prepare system which would be controlled enough to know that you control the parameters that you would like to control so in your case may be, would be
09:00:06 binary or sickness, you will be maybe the right protein so one of the big problem is to get the right machine into the membrane, which has been a really one of the limiting limiting factor to, to, to have this feeling progressing, because it's not easy
09:00:32 protein and to have the right protein and to control the protein. So this is one, you can have a lot of practical issue to get the right system and control. And then the other question is what you can measure right.
09:00:37 So, and.
09:00:38 So, so far we were discussing experiments where people were measuring spatial correlation, or time correlation.
09:00:45 They were doing, for instance. Image Analysis I mean looking at instabilities etc. but maybe also, you could learn something by measuring, I don't know diffusion.
09:00:57 Or maybe there are there are many other experiment which could be done but but the problem is, what you can prob with experiments and what is what scam you can go What is, what in what I mean, how precise is the model, and how I mean, what is what is,
09:01:16 but like the problem is, is never so simple, because the experiment a little bit limited difficult.
09:01:24 And so it depends. I would say, it depends on what. Sometimes I discussed with Giambattista for instance that I see in the audience, and he has. He's coming he predicting very nice effect on on long reign in some cases and he came a few times to see me
09:01:40 and say Patricia, is there a chance to predict that and I said, Well, if you want to say anything by 10% maybe it's really narrow path of the regions which is a very, very limited so I think this is exactly the point, if the effect is big and, and it's
09:02:05 Thank you. I just had a quick sort of follow up comment for rich if that's okay or I can come by oh yeah yeah yeah.
09:02:13 Okay, so rich I very much enjoyed your talk, I wanted to I'll post a paper on slack I just wanted to say that Sylvie Rocha EP FL, has been doing some very nice experimental measurements of ions and liquid bio layers that maybe could be relevant, I don't
09:02:32 know how yet. I'm just looking at random connection so I'll post that I just wanted to say that I very much enjoyed. Oh, thanks.
09:02:41 I'll read it. Thank you. Thanks.
09:02:44 Alright so now we can go to, Alfredo.
09:02:59 I guess it's another Patricia question, and I should I want to do it starts from things we discussed here in there on slack and even here maybe starting and also from our Matt's question but I wanted to like flip the issue and say, measuring the spectrum
09:03:07 or the time correlation or whatever we want to measure, what do we learn, not about the membrane but about the active system that we are encapsulating or incorporating in the membrane.
09:03:20 Like, naw Kham Can we just looking, I don't know what's in my bicycle I measured the spectrum, what do I learn.
09:03:29 You can expect maybe to, to have some signature about if you have, so there was this experiment from, from even Lopez, in Madrid so basically with this rotating protein, he was able to, to, to, to extract from the filtration of modifications, the time
09:03:44 correlation. So you really measured the time correlation he really find a signature.
09:03:50 Where, where I find a characteristic time which was corresponding to the rotation of the, of the motor. So you could have also signature, maybe, depending on the time scales if you have a protein which is a really flipping at milliseconds rate, there
09:04:05 is no chance. But, but if you have a molecule which has a, it's a characteristic time which is accessible with, with a filtering technique, you might be able to get to get some say some, some time for the, for the active process.
09:04:23 And by simply repeat my question but I limit myself to the flood to the spectrum like this.
09:04:30 The the amplitude fluctuation and not the, um,
09:04:37 once you're done, I mean that that you wouldn't know from, let's say a structural experiments or something like that. I mean that's that's the worst case of course I would say, I would say, at some point, if the protein, the protein.
09:04:51 Change really formation and change shape. So basically following on behind that question. So if you have something going from that to that, in principle, you have, you should have a signature, one way or the other on the, on the spontaneous curvature
09:05:07 of the membrane, which is related to that so you could you could really have effect which results from that which could also result by, let's say,
09:05:18 yeah, so maybe, maybe, maybe somewhere in the in a in a situation spectrum you could you could get something about this, this, this change right. I don't know I guess we need.
09:05:28 We need modeling, a lot for this kind of. Yeah. And then, and in this case also, you might need also to get. So, for sure. For sure the special coronation of the situation spectra and the tongue coronation one give you will give you the same the same
09:05:44 type of information so I think, to get both of them on the same system would be great.
09:05:51 Maybe a question related to that to Richard on one of your first slides you were mentioning that some of the constants you need for your energy for your charm whatever is is obtained by flickering.
09:06:13 So, I have no ID, so it's a bit related to this question so you use recurring of the IP to membranes to derive the pending muddiness is that right.
09:06:36 I mean, no, but what we calculated, a
09:06:41 bending modulates using a frank rounds a tick tick tick tick tick tick tick tick director fluctuation on a simulation size violator, which is only around 600 limpets
09:07:00 got that. And then we compared it with, with the experiment. But, But this was after the force field.
09:07:12 I'd already been
09:07:15 developed so it was more of a validation of the force field, and and and and when we did that it turned out that that for the limits we tested, read very well with experiment.
09:07:30 So, we didn't actively use the X the experiment to build force field, we just use that as a validation. One of the things we were interested in.
09:07:54 glass of water.
09:07:57 It's a subject that that that that john Daigle brought up, and it says, when you look at the bending constants that were derived from from like pipe that asked for aspiration, about
09:08:12 The X ray scatter and like flicker. At first, the bending consonants from pipe and aspiration and X ray were actually quite close and they were only about one half the values from from from from
09:08:37 from the flickering.
09:08:39 So, so the fact that, that the simulation seem to agree so well with the flickering.
09:08:45 We were happy about that but but look kind of worried because it didn't agree with the others.
09:08:53 However, then john included.
09:08:58 The, the, the tilt module listen in the interpretation of experiment, and like his values, then became
09:09:12 very close to those of the flickering experiment. So, we were, you know, happy about that. And, and until modular that we're out there. We're also pretty close to John's, but this leaves, open, open the open the question is, so why the bending concepts.
09:09:31 When the pipe that aspiration are only about half those of like liquor.
09:09:37 I mean john might
09:09:40 want to say more on that. If you would like to I suppose but but I think that's an important question it like bothered us that the numbers work by so different.
09:09:54 I wonder if I might comment on that in context.
09:09:58 So, thank you rich for for pointing that out and it is interesting because our numbers did go up for the Denny modules and we included the short range effects of tilt modulus.
09:10:10 Now I might also comment that that my colleague, Mark is the center has continued to find that you need to include other things.
09:10:21 In the short range scale, and that could also change the numbers again.
09:10:26 When we analyze our data so the question is analyzing our data using better models, rather than just pure health race using help nourish plus causal up.
09:10:36 And now maybe plus the Santo as well. I'll say that, and this is work that's ongoing with with with Marcus is one of the markers as students, I'll say that right now it doesn't look as if, including what Marcus is bringing up is going to change the bendy
09:10:52 modulus, but it may change the tilt modulus, so preview of coming attractions.
09:11:01 However, The way you're analyzing Frank Browns data.
09:11:14 Fire where you're analyzing using right rounds theory is still using essentially the, the tilt modulates but not the not Marcus's thing. So, so that's.
09:11:16 Sorry to interrupt here and get out of turn I did have something else that I wanted to comment on with respect the rich but I'll leave that later and I'll stay on the line and maybe make that comment lender.
09:11:28 Okay. Right, thank you very much.
09:11:30 Next question by Ronnie, Ronnie Ronnie, are you with us.
09:11:37 Yes, just.
09:11:41 Hello.
09:11:49 So actually this is related to these questions on how to measure, better.
09:12:01 The actively men brands.
09:12:05 So I actually was impressed yesterday. I met in this town, virtual town, a guy who published the nature article on correlates within a physical. Oh, he's here.
09:12:20 And he has a very nice measurement of the spectrum.
09:12:25 It seems like he gained one one power of q. So, so, maybe, maybe that's that's something to look forward for for the purely active member, because in his system that activity comes from the, from the back from inside.
09:12:46 But I want to bring something that I was involved in a long time ago.
09:12:55 Paperwork which is almost not cited there but nevertheless.
09:13:02 I think I think it was a good proposition at least, and it was to measure.
09:13:08 What I always liked the member name is see take next segment, MSC or the equivalent is power spectra influence space.
09:13:21 And we're very nice predictions, and then we're based purely on the original model of boy invoice my so I know
09:13:32 you will alter this model, quite a lot of the words, as you also mentioned in your talk, but I I wonder if anybody tried to actually I would like to share the screen.
09:13:46 If I can
09:13:51 bring some, just to show.
09:13:55 So by the way this is this is a, do you see the screen. Yes.
09:14:00 This is life day, the auto correlation function we calculated. more than 20 years ago.
09:14:07 For the problems my soul used to large peer mediation and this is the corrections that you can make to this. If the emotion is negligible. As you probably know, but actually I wanted to mention, M is this like these kind of MSP which us maybe a exaggerated
09:14:37 And I'm not trying to blame for that but it's like I took some values, and maybe they were wrong but what you see here for example is the two the two thirds which will translate to omega to the minus five thirds that people do see in power sector, I know
09:14:56 that.
09:14:58 I think there's two sides to it.
09:15:00 So here, for example, there's a, there's an exponent which is attempting to be maybe five thirds, but it's not quite because it's bound by this bound by the other regimes.
09:15:14 So basically, it's trying to catch, catch all those which are related to a certain process. In the membrane.
09:15:27 And we could distinguish in theory, of course, but in reality of course it's difficult like the diffusion part always give up to the five sets in this model.
09:15:38 In this model of large formation. So I just wonder. Have you ever tried to do power spectra of active member and why why why is it too difficult, so difficult.
09:15:53 Know It turned out that we will have to do it better.
09:15:59 And the fact is that, as I say, there was not so many experiments done on it moment so there is no good reason not to do it, but I would say as I know that there was also paper from channel so from two years ago, also doing some prediction about, as you
09:16:14 say, an ns diffusion or perturb diffusion, but we never did it so I think there is no good reason not to do it, but so what I'm not sure is we get the maybe the time resolution, good enough to maybe to see all the different.
09:16:30 Let's say different scaling laws but I would say, this is something which has to be done for sure, with no good reason not to do it.
09:16:40 But I mean as far as know, maybe somebody in the audience did it I didn't publish. So, this case, I don't know but
09:16:51 we did see we did see with Timo bit some changes in the slope in red blood cells and in in physicals where we change the parameters, higher so vital. Oh, sorry, to hire soap.
09:17:10 Yeah,
09:17:13 absolutely.
09:17:15 Yeah, I need to, to look at this, we interpreted it in, in terms of
09:17:24 dependencies on.
09:17:28 I mean the port power of.
09:17:31 Was it t. So, so I need to look it up but we can discuss that.
09:17:38 I need to be.
09:17:40 Maybe we can discuss that outside this.
09:17:44 If I can come in very very quickly on this.
09:17:47 So, I'm not sure I got the paper you're referring to, but there's a couple of very fresh ones with one with propel particles and one with the bacteria, and I think they all see a difference low but the low mode.
09:18:02 And now you also see something like that we are these cycles skeletal bundles moving inside.
09:18:09 And in the bacteria paper which is linked in like a couple of times here in there. they have a model where they knocked the force with a given correlation time and they sort of predict the different low but low mode.
09:18:25 So that could be a starting point.
09:18:30 I think we would need to review these different soaps.
09:18:37 Right, Ronnie, are you done.
09:18:41 I can talk about.
09:18:47 So I suggest in.
09:18:51 Thank you. And thank thank you Felicia for the workbook. So, I have some other kind of naive question which is, I'm just picturing that, you know, you start experimentally for a balance of similarity between the juvie and the solution.
09:19:10 And then you start importing aliens into the jewelry.
09:19:14 So therefore, you would expect to have a, an awesome well it must balance, and then a way to compensate that would be to have an influx of water so you got it, which would somehow, you know, swell a little bit, or I don't know, the, The, the juvie, right.
09:19:35 So, yeah, so I think the fact that we have.
09:19:38 So in the case of Dr Dobson for instance, we, we, we have in our gv nominee we have protein reconstituted symmetrically so some are pointing towards inside some and half pointing outside.
09:19:52 So, in case of bite your lip syncing to activate the protein.
09:19:57 Let's say all together, I would say, we have maybe a net flux of protein which will be very limited. And in this case, the difference of us much pressure will be very small, even in the case of consumer GPS.
09:20:14 We, in this case we have a teepee outside, so there is a flux of calcium through the inside so you're right that would be a small change of iron but but the concentration is changing very very, very small.
09:20:25 So I think it could be a contribution from that but but considering the volume of the physical is is big and the number of ions flowing per unit of time is also small is like a 100 milliseconds at the end of the day, I think this this is not probably
09:20:44 very, very important. And there was a question on slack which is following on what you said that also we can create a different of transmission potential, because now we have an imbalance of violence and.
09:20:57 And this is true. And I would say so again this is probably not important for biopsied might be important for customer GPS and this might also.
09:21:07 It can also influence also the activity of the park because sometimes the pumps and really the activity is reduced. If the pumps now against a membrane potential.
09:21:18 This could be important and this also could contribute to the system. So, you're right. And this is something which is a difficult to I mean we are, we have to live with it clearly.
09:21:29 So maybe by Yeah, we can be. We may be by changing. I don't know the ATP concentration I think we can maybe, this, this, let's say, Maybe it's possible to kind of
09:21:43 find out a way to to to separate the effect but there was much pressure with pumps is low, if you have if you have channel it will be anyway. You cannot just do this I don't have much better.
09:22:02 graduate is dead so anyway. But you're right. With the small effect.
09:22:04 Yeah, but when when you use the micro pipe it does the tone length, change the course of the experiment
09:22:13 experiment is very quick so the noise.
09:22:16 So I mean, basically everything is done in a few minutes.
09:22:20 Okay, so I mean, so I like that time I don't know, be important. Okay. Thank you.
09:22:30 Okay, maybe the next one is Marcos, as an organizer, he has a priority.
09:22:35 Oh, my goodness.
09:22:38 I have a question for rich, I would like to come back to the pic clusters that you simulated in your membrane mean, these are these are interesting simulations, but they're also of course very challenging to do this this system is so big and you'll have
09:22:52 to figure it out how things really great.
09:22:55 I think on slack I suggested one way to cut it down dramatically is just to simulate like a primitive electrified model but maybe that's too brutal. So I was wondering, what if you run a simulation where you basically just a candidate for the little bit
09:23:08 head groups, forget about all the tails just somehow pin the head groups to some bass playing using the implicit solving model for the water and then put the the take potassium and calcium in there, much bigger system and you can explore over ranges of
09:23:22 concentrations with designs would go and how they would know compete against each other for binding.
09:23:27 Would this be something that's useful or is this just too highly simplified given given what's going on in that system.
09:23:36 No.
09:23:41 I mean,
09:23:53 that I think is, you know, a, you know, a image.
09:24:00 it's not my style, but I think it's fine for people to do
09:24:03 But, Ted where she has a you know head only model, where you know he has a clip tale clip as entails what I don't like about the model for, you know, the kind of detail work.
09:24:17 I like to do is, you know, has very little way of getting a spontaneous curvature, which is something I'm interested in.
09:24:28 And, you know, I just find that the, the implicit models.
09:24:51 Don't give the details. I guess I always felt that my role in all this is to do the, do the best all Adams simulations that I can, which takes full time really and working on the force field.
09:24:56 And I'm very happy to give anyone else, a trajectory is that they can use for a simpler model, which we really need to do to reach that Ireland scale.
09:25:11 So that's one of the non answer I realized, but it's just not what I'd like to do.
09:25:21 But thanks. The question.
09:25:24 Okay, thank you very much so maybe we could go to put a prayer, who didn't ask a question yet.
09:25:40 Hello, Patricia. This is a question for you. So I just wanted, I had a very nice question which is what is the what is the concentration of proteins and the cell surface.
09:25:51 Depends on the surface but I would say at least 40 60%.
09:25:56 Okay.
09:25:59 Yeah, but so these if I, if I take them as sort of little discs. Okay, very, very simply, that would be what a few nanometers in
09:26:13 between them. So I mean, the membrane is crowded Yes, but I don't know what maybe, I don't know.
09:26:26 Yeah, so I'll tell you. I'll tell you the reason why I'm asking this question so there's been a lot of thing a lot of discussion on Slack, saying that.
09:26:35 Okay, well there are these active processes which actually cause things to cluster.
09:26:41 So, from an earlier paper I think it was about 93 by Robin brain smile and Mongolian where they talk about fluctuation induced forces on membranes even just runs, and that that could bring those two together.
09:26:56 And I think the strength is of the order of its some constant divided by out to the bar for.
09:27:03 So
09:27:05 for these passive fluctuation induced forces. Then there is of course the, the recent work that I think was also mentioned on slack which talks about a one by r cubed, kind of power forces which comes from activity induced motion I haven't read the paper
09:27:25 very carefully so I can't talk about that.
09:27:36 The question of course is then why do you know presence of all these active forces, why don't proteins all come and cluster together.
09:27:39 And, you know, it's just trying to do something again back of the envelope calculation to sort of try and compete because one of the what, when you cluster.
09:27:46 The thing that you lose is basically the entropy.
09:27:50 And so a measure of that would be something like give at times log of the area that is available to you, divided by the area of the, of the individual protein or something like that.
09:28:01 So I don't know I mean that's why I wanted to so I'm getting some length skills from that and probably they're all just rubbish but just just want to wanted to wanted to get some idea of the so it's probably some nanometers and the other would be from
09:28:14 microns or the cell radius, or would be.
09:28:20 Oh, you're basically radius would be what floating icon for my friends. Okay. Okay, so that was that.
09:28:29 Yeah, so that was the reason why I was asking this question so.
09:28:34 Okay. All right, so I'll probably get back to you in with some numbers and you can tell me that they're all wrong.
09:28:42 Maybe.
09:28:44 Two more.
09:28:46 Go ahead.
09:28:47 I have one small questions to richer richer richer.
09:29:10 with them with account with a test him, or
09:29:17 the investigation of hydrogen bonding was is the answer.
09:29:23 Right.
09:29:32 I think that the effect is that.
09:29:34 Is it the, is it the first axiom cake.
09:29:42 Is it the.
09:29:42 I can bind to that actually the one position to the BuzzFeed one, which is the one on, on the glycerol chain.
09:29:51 And then the calcium can, I can then bind the to the phosphates on the ring.
09:29:59 I think it because a damaged charges. I think it's harder for the calcium to to get near the violator surface and bind to that upper to that.
09:30:16 To that glycerol phosphate.
09:30:29 I'd also like to add that we have some new results that were, you know, given after the central me after my talk, I can show you there. I'm pretty excited about them.
09:30:31 I'm sure I can have them here.
09:30:42 So,
09:30:49 this is lifetimes,
09:31:05 symbol is the calcium,
09:31:11 less than, plus the bus bus, the bus, the bus, potassium, and I'd like to emphasize that there's much less calcium here than in this one year. This is about $150.
09:31:12 clusters, and, and, and the end and cyan
09:31:29 million dollar, whereas the calcium.
09:31:29 in this system.
09:31:38 million.
09:31:38 So you can see really clearly there are diamonds and triangles and everything else.
09:31:43 The one that's that these ones with these mixed systems are much more stable. So this is, you know, I don't obsess kind of stuff.
09:31:47 In the vault is only about $25.
09:31:53 So, it's,
09:31:57 it's this
09:32:02 combination of where the lions, go there I think it gives that synergy
09:32:12 up
09:32:15 either not hydrogen bonding.
09:32:18 Ah, I see. And, could it be the character of double charge, I mean the counselors, double charging. Sure, yes.
09:32:42 I mean calcium is an international minder in the language whereas, whereas potassium, is it is outer shell in the language of
09:33:01 Collins specific line affects me calcium is a cosmic tropic potassium is a.
09:33:01 k. a tropic.
09:33:03 It's just know that calcium will will like form clusters with stuff. Yeah, whereas.
09:33:08 Whereas, whereas like a fantasy mode, and that includes a DNA and proteins as well. So that's why you have
09:33:23 potassium, inside of your cells mostly and not a lot of calcium away bed thank nice and then the same way.
09:33:36 They are the double charged ions. Yes, but but it's the same thing is that, magnesium in Collins
09:34:02 is a specific I in effect is actually more like but just experimentally it seemed that I guess it's a outer shell as well although I'm not positive about that right this moment, it just so there's different sizes of ions, it's not just the George, I see.
09:34:14 Thank you.
09:34:15 Well, Thank you for the question, thank you john.
09:34:19 Your turn.
09:34:20 Yes. Can I share screen I think I'll just want to show you a question that roomie had that we didn't we, so you can see it here this is roomies question we dealt with the first part, special dealt with the first part but
09:34:56 lost john think we did. Yeah, we, we lost.
09:35:01 I wasn't sure it was on my side of what that maybe we can read the question.
09:35:09 Ruby Can you read your question.
09:35:17 I think this was about area right
09:35:23 answers because john appears because Stephanie also answered this question.
09:35:42 Yeah, Stephanie had some comments Yeah, we could maybe discuss it later when john switches off.
09:35:42 Okay.
09:35:42 Okay, so how mad.
09:35:42 Yeah.
09:35:44 I have a question for you, regarding that it's, um, so I think Vinton falters sure beautifully that if you have that single negative lipids, you have an increase of bending rigidity and then using experiments we were able to prove that, what would happen
09:35:59 with that, I guess. Like, how would the bending rigidity, modify, maybe I missed this point from you.
09:36:07 Yeah, I mean with the, with the small amount of
09:36:16 effort that that better into by layers.
09:36:21 I didn't change it too much.
09:36:24 In the minor layers.
09:36:26 We, we didn't calculate bending concepts per se,
09:36:35 but the the area compressed ability, really went up
09:36:44 with different ions.
09:36:48 That's a supplementary information that monolayer paper, but but it's like really quite huge, so it just makes it more stuff, for sure. And so, if it makes you know by the rough correspondence of the area compressed ability and abandoned Garson.
09:37:11 If you have a lot of to in, in, in a cluster.
09:37:16 It will make it more.
09:37:17 The violator more of Richard has to be whole lot, maybe more than, like the five or 10% that you see.
09:37:29 Okay john you're with us again so can you repeat your question and so it was about roomie, and Stephanie and your microphone is off. Yeah, so I'm curious I got cut off as soon as I tried to share the screen to show what roomie had had asked so I'll try
09:37:46 to just paraphrase it, it was a it was a very general question but one that I think is, you know, I'd like to just make a general comment about so she was saying.
09:37:57 After this was regarding riches talk.
09:38:00 He was she was wondering about the area per molecule and then getting into interesting questions about. First of all, a symmetric membranes and also what does it mean to talk about the area of one lifted and not the area of PR lip and in particular, when
09:38:22 you have mixtures and you have a charge to like rich had. What is the area when if it happens to be surrounded by other tools versus being isolated and questions like that which are very interesting questions, especially for for modeling for doing theory,
09:38:35 but there are questions that I think are unlikely to be answered experimentally. So I think the synergy between simulations and experiment here, and I think Richards already said this obviously made this point in his talk.
09:38:51 Is that what we try to do is to give him get as many experimental numbers as possible, so that the simulations can make sure that they're working. Okay.
09:39:02 And then the simulations can give this kind of information that room is is asking about in this in her second paragraph in that talk. So this is, this is probably old hat and obvious to everybody here, and I were just saying that.
09:39:17 Maybe you will indulge me as perhaps the most senior member of this, of this conference to be able to make an obvious general comment like this, but I think that this is the is the synergy.
09:39:30 The very valid and important synergy between simulations like what riches doing and experiments like what Patricia and the rest of us are doing.
09:39:41 And that's it.
09:39:44 Thank you. Thank you.
09:39:46 So and.
09:39:50 Yeah, hi. Excellent talk by what can you, can you hear me.
09:39:55 Yes.
09:39:56 Yeah, so this case. Thanks for the talks.
09:40:01 I really enjoyed them.
09:40:03 This question is for rich. So, so when you have these people up it's, it's there, they can have this different ionization states right and not just the ionization state but also for donation states like for the same ionization you can have different philosophies
09:40:25 to donate its. And so we seen some of the simulations that we have been doing recently said the potential of mean force of protein binding to the membrane with two changes.
09:40:39 In some cases, noticeably. If you have for the same ionization state different protein nation states.
09:40:44 And so the question to me to you that I would like to understand is that is there a way I mean an experimentalists can chip in on this is there. So imagine like aren't getting Canada's have tried to study this imagine that the people if it exists in multiple
09:41:06 ionization state as well as multiple nation states.
09:41:06 And you were trying to do an exercise where you're trying to find the populations of this in a given by layer right. So, so you use, and this can change with different Ph.
09:41:15 So how do you.
09:41:17 If you have to do such an experiment.
09:41:21 And, and if this is a good question to ask. That is the first thing that I think you should verify because I may be just thinking about it wrongly, what would be good experiments to actually get these populations and in simulations when you are actually
09:41:35 doing this.
09:41:36 You take a single ionization single proto nation states and and run the violin simulation. So how would you. How should we like interpret these data from the experiment that the real more realistic system that's what.
09:41:53 So if it makes sense to you please do go ahead and humor me otherwise. I mean, I'll just assume that it's a question.
09:42:00 Sure, it's an important question.
09:42:04 Well, as, as I guess, you know, and most everyone.
09:42:09 When we currently murder simulations, but we actually just have to fix the nation states.
09:42:28 Those are the choices vision and shift a little bit, but not that much, But the next, you know, kind of simulations that will be that people are working on is actually what it's done is a constant, a
09:42:48 pH simulations, where the nation state actually can change in the in the simulation.
09:42:56 During the simulation. But those are the very early stage right now and they're not, you know, that sort of ready for prime time. I'll just say, so this is another thing that you know in in like five years I think this will be a routine, but it's not
09:43:15 routine now.
09:43:19 I've been experimentalists, I guess can measure proud nations dates.
09:43:27 All kinds of methods. I don't know that much about it though.
09:43:30 But But I mean, we've we've, we've, we've for the ones we use we use the ionization and the prod nation states.
09:43:37 What you know corresponding to do,
09:43:41 to a pH seven or experimental friends tell us you know do this we say yes. Okay, so that's okay. I hope that same thing. a good enough and that that.
09:43:53 Thank you for your question.
09:44:02 Right, I'm Morgan.
09:44:07 Yeah, hi.
09:44:08 So thank you very much for for this is very nice thought.
09:44:15 I have maybe more like a context question.
09:44:18 I guess maybe more for position but, Richard.
09:44:23 Feel free to answer.
09:44:24 So, all this, it membrane physics is definitely fascinating.
09:44:31 And I was wondering if we know any repercussions in the biological world.
09:44:37 If we have any example of whole active on Brynn, maybe a cap, Madrid he was touring, I don't know if in PTP depraved Sarah's or if the bending rigidity or tension could affect an offer gf organelles.
09:44:56 If the activities module at some point in the cell.
09:45:01 I don't know many examples I was wondering if you knew some, be sure.
09:45:09 I would say something which could be used by the Center for its function right so i mean man.
09:45:19 I don't know I don't have that I mean, I think that might be useful for our vision. When we miss what we need, it's possible this is the foundation of London.
09:45:31 When it's active are affected by by the by activity you could imagine that the way that the sand will approach and as I said we're approaching a surface can be affected by by the activity.
09:45:45 And that's one example.
09:45:48 And it's not clear yet because our model telling that the future should be enhanced and there are some of them said that filtration to be, let's say, flatten so near near near wall so it's not so clear.
09:46:01 So this could have influence.
09:46:05 Also this also could have an influence after that also on solid on the clustering of proteins.
09:46:12 But I would say really directly on the function of the cell I'm not sure that there is anything which has been described on this term so far, besides flickering of red blood cell and I think that says in a comment on that but they say flickering or red
09:46:26 blood cell which now is clearly religion in really related to activity. So I don't know if it has to do with this function but at least you can relate the rent the property of the active Marina what you observed.
09:46:40 And depending on the activity but for the for the same function. I'm not sure that has been.
09:46:46 Let's say considering this term so far
09:46:51 that you should.
09:46:56 I don't know anything, very specific to add, but I just know from roll.
09:47:14 Oh. The path to being involved in everything. So, I imagine this some
09:47:24 Stupid locklin's to watch that video which was a slide.
09:47:25 to clustering.
09:47:27 clustering changed the local properties, the membrane. And, you know, might make it more
09:47:37 amenable to do all kinds of
09:47:40 the remodeling, but that's very broad not specific. Sorry.
09:47:46 Thank you.
09:47:48 Thank you, Peter.
09:47:52 Yeah, I have a question to which sorry if I might have missed that during the discussion there was a question on slack about in our does the imbalance of violence, translate into appearance of transmitting potential in the simulations, and how big is
09:48:17 it. And the reason I'm asking is because usually transparent potential is linked to appearance of an effective tension. You know, I live manufactured and this could also trigger some morphological changes in the memory.
09:48:22 Yeah, you know what,
09:48:29 when I saw that question first.
09:48:36 That it was referring to, if, if he is we're actually
09:48:46 maintained to like be on one side by, you know, a potential or say an extra compartment, and I answered the bat that that's not the case. And I can, you know, you can sample both sides, because why the periodic boundary conditions.
09:49:08 However, then I thought about it more and I don't recall. If I stated that should change.
09:49:15 I mean, the men, the Bible as we mostly suddenly a race a metric to this only PIP on one side, that probably should should change dipole potential, and we'll make some changes, and I'm going to calculate that now.
09:49:35 So it's a very good suggestion, where you know whoever made it might have been do I just forgot, I'm sorry.
09:49:49 Celia, so I think question for everybody who wants to answer. And there was a very active discussion on slack so Cecilia, you are the leader.
09:50:01 Thank you. it's the field for, for, for, for allowing me to to ask the question. So the question was already addressed by Patricia and others in the slack and it relates to to some experiment that we are very interested in, and has to do with measuring
09:50:19 transformations. As you know, as they are cure under membrane activity or in particular actually broken pumps. So, but maybe I can use this time to pick on everyone else's brain, in addition to to Patricia, which is, how do you expect that member and
09:50:39 activity willing packed transformations and specifically the formation of pores member infusion and pours.
09:50:50 Yes. So, you know, we know it affects bending rigidity intention, but how about transformations.
09:50:57 Anyone has some clever thoughts to share
09:51:02 ahead.
09:51:13 So maybe Cecilia you give some examples of these transformations you would like to have reactions on. Yeah, so, so I can tell you sort of the specific experiment we are interested in is that it relates to to escape of liquid nanoparticles from, and those
09:51:31 normal compartments and we know that the process starts with the ATP is pumping proteins, into the, into the end zone.
09:51:43 the onset of member infusion and formation of a poor.
09:51:56 And so, you know, we, we, we know that membrane activity, you know, it seems to reduce the bending rigidity of of the membrane of a gv, But, you know, how does that impact transformation say formation of a poor or, or even, like, you know, even just pulling
09:52:19 over to you know how how that impact will it, enhance transformations or will it suppress transformations you know what's the sort of the expectation
09:52:40 and Patricia talked about line tension.
09:52:45 And so, so that was sort of related to that discussion a little bit, but I don't know if anyone has would like to add anything you want to answer this, or.
09:52:58 Yeah, just to just to just a small comment saying that if you, if you, if you want to look at the membrane fusion processes where you know you've got two leaflets which are coming together, and the initial stage where it's deforming and, you know, trying
09:53:17 to fuse.
09:53:23 You can to an extent, get to that by using continuum theories, but where the membrane basically fuses and you form a poor that part, I kind of wrote, sort of, say, good luck with elastic theories and getting that because you know you're not going to.
09:53:41 You built there are things happening at a much smaller scale at the level of liquids basically rearranging from the two leaflets to basically forming a channel or a poor, and those probably fall within the realm of more to do with simulations, I, that's
09:53:58 probably not answering your question but I'm a better fingered theorists So,
09:54:05 so that's that's all I wanted to say, basically, if you have holes and stuff like that there are there are other. There are other things that you need to incorporate for example.
09:54:19 Exactly like my intentions and on vanishing line tensions and things like that, even when you're continuum theory you need to incorporate that to host I don't think the.
09:54:29 I also don't think the goal, Goshen curvature integrates to constant term. So, If you are in the presence of holes. So there are some considerations to think about that.
09:54:39 Right.
09:54:44 You want to add something on this.
09:54:47 We can't hear you
09:54:51 better. Yeah. Hello.
09:54:54 I'm embarrassed to say that I don't really know what slack is but but I did the Bicentennial and I was able to do some experiments on tension and fusion, and in all of our hundreds if not thousands of experiments we needed to increase tension to see complete
09:55:15 fusion, this is of a faster leopard vessel to a fossil leopard plane or by layer at constant BLM type tension.
09:55:26 Guess point 1% or something. So, under those conditions we had to add more tension with us Malik pressure on the, on the vesco swelling the rascal to get fusion almost to the breaking point.
09:55:39 Then when we dug in much later with Mike. Mike my cross could be simultaneously with this electrophysiology, we were able to see two different we break it down into the transition to lip and mixing, which was relatively unaffected by tension, and the
09:55:56 trend and and and we saw for the first time small flickering course, the higher resolution. Moving to these unbelievably beautiful objects known as the gv.
09:56:14 And when gave us much better signal to noise obviously going from my basketball gv to a by layer instead of 100 nanometers classical to a Byler. And there we saw clearly that the major effect of tension was to carry the flickering fusion pour all the
09:56:27 way to are irreversible.
09:56:30 Complete fusion state.
09:56:32 And we have some information or papers about the liquid dependence on those phenomenal.
09:56:38 So, so I'll look for those papers thanks so much for sure that's super helpful. Thank you.
09:56:47 Okay, thank you. So is there a burning question in the last few minutes. Otherwise, unless my pocket question
09:56:57 right so let's do so.
09:57:01 In fact, Richard. You mentioned that tip to is very important for consumers relations.
09:57:09 Right. Oh yeah.
09:57:15 could you
09:57:16 allow me that sperm cell clean.
09:57:19 Yeah, exactly why we're here.
09:57:23 Yeah. So, in fact, could we image in some, some simulations and experiments on tip to membranes that would flicker through calcium oscillations.
09:57:41 I mean close to pumps or whatever, what what could be done with your customers relation to be able to see it with an experiment that Patricia would do.
09:57:54 Well, I mean we actually had a calcium isolation, in, in the simulation, it's maybe a little bit contrived but but one Kansas.
09:58:12 I mean, add calcium, up to the bulk and then simulate it. In fact, when you do that then you see
09:58:23 the 15 clusters. But I think what this actually was with a, you know, a example, I like news.
09:58:33 It was calcium
09:58:38 pumps that were that were turned on by the by the festival lipase
09:58:47 cleaving the pit to into the tails, plus they notice the head, then that you know bound to some pump and that's sort of the isolation. So I'm not sure how much.
09:59:00 I mean, to was involved in that. But, except, except for the initial sacrifice of its head.
09:59:10 So, but yeah it's a. We're also trying to look at, you know, systems of.
09:59:24 I mean, another very interesting system is when, when an appeal the two is attached to a liquid order.
09:59:41 the, the PLD to, or, or a general anesthesia can somehow melt the raft a little bit, the, the, the PLD to a tendon.
10:00:18 then find the channel channels, and then Cause you know cellular function.
10:00:24 So there's a lot of things where one can start to look at those more complex systems.
10:00:30 Exciting, so thank you. There's a lot to do on reconstituting active membranes. Yes, Yes, yes.
10:00:38 So, I think it's time to stop. Do you want to conclude one of the organizers. Yes, thank you so for, you know, for moderating this another lively discussion and thank you also to all the participants for, you know, being very very active, both on slack
10:00:56 and in these, you know, some discussions.
10:01:01 Also, I want to remind you that you know we don't need to stop here you know we encourage you to continue discussions on slack to encourage you know separate meetings and get our town on zoom or wherever you would like.
10:01:12 And next week we're going to switch to a new topic we're going to talk about extreme mechanics.
10:01:18 We're going to talk about meeting Kia gummy wrinkles and all of these many
10:01:24 different events in inelastic sheets and you know the three of the four talks are already uploaded so you're welcome to reach them watching them the last one will be uploaded today.
10:01:37 And then you know you can already start have discussing them.
10:01:41 In the second in another channel devoted to the second week. So we're going to share these will going to send an email to the mailing list so that you, you know like where exactly to find it.
10:02:02 So perhaps adding also that this Monday there'll be another meet and greet session and those of you that have not introduced yourself so please come in and meet to the speakers of next week and the chairs and take a little time to introduce yourself.
10:02:17 Looking forward to seeing you there.
10:02:21 We also have a informal get together tomorrow, but that's at the time which is more user friendly to Europeans and Asians.
10:02:30 But still, Americans our to join
10:02:39 in America is also welcome to schedule impromptu like informal meetings at any time.
10:02:44 And not just a madness any anything.
10:02:49 Alright and enjoy the rest of your day and we'll see you soon.
10:02:54 Thank you guys so everyone.
10:02:56 Thanks for your question.