 You hear me in the Zoom, because you can imagine this is the first talk of the lecture of the school and we are seeing these Zoom problems, but it seems now that's fine. So welcome everyone, again, the school of information, noise and physics of life, and I try to welcome you. So I will start today with giving an introduction to biophysics. So Benimir explained that he said wrongly that I'm a world expert in biophysics, it's not true, I work mostly on non-equilibrium thermodynamics, but applied also to biophysics, biological systems. But we do a lot of activity also in biophysics, in particular, we have a course in HPP dedicated to this topic and they are trying to give you an overview of what is biophysics, why I find biophysics interesting, and what type of physical, what can physical or mathematics do about biological process. It will be an overview, so I won't give many formulas, it will be practically zero formulas. So I start a bit with motivation examples and focus on biophysics. Why do we do biophysics? This is a sketch, because we can see cells, biomolecules under a microscope. So one, two centuries ago we couldn't see our cell, bytes at the scale of nanoscale, now we can do this. And also we can measure physical properties of biological systems. Before it was just pure observation, which was the discovery of DNA, crystallization of DNA, and you could see these mates. I would kill this fire, but I was just visual, it was not about forces, velocities, etc. Now, thanks to the experimental techniques, we can also measure physical properties of biological systems. Here I show some examples. You can see microscope, human cells, and then there's a microscope, you can see. Here it says, please record, so that's to be me. No, we are recording. Okay. And these are the human cells under the microscope, and you can see the typical size of human cells, around 110 microns. And just to remember some of you, you may not remember, a micron is 10 to the minus 6 meters. So one meter, then a one million microns. This is an example of bacteria, which is another cellular organism, which has a size of around one micron. Of course, keeping in mind that not all human cells are the same. This is something you love to keep in mind. I don't know if you are a biologist or not, but it's not the same manuron, which is a cell that is like wire, with a small body and a very long tail, than a red blood cell, which looks like this. So think about this, the human cells are different, but the range of sizes is different. And here is an example of a virus, which we know very well, unfortunately, which are much smaller. You see here, this is the scale, which is 0.1 microns, so they are on the size of none. So most of the important, relevant, biological processes happen at this scale, very big time. They say, this is the size of the cell on microns, but we could go biophysics at different scales. We could look cells on its own. We could put inside and look at organisms, and part of the cell, which are smaller than the other, even microns of bacteria. We could go smaller, like a virus, which is a nano. We could go even smaller, smaller, like a protein, because of the other nanometers or lipids, less. Or even do biophysics at this level of the single molecule. Scientists who do biophysics, our molecule binds to another one. As we know, for example, in this current pandemic, it's very important to know how a virus attaches to a cell. This happens at scale, nano, even less, atomic. So one, as a physicist, could attack biology at different scales. So we can tell the lab, and even beyond. So maybe you are interested in knowing how birds fly, and how they make groups and flocks, and that's even bigger. This is Elphameter. So I say, we want to introduce biophysics, because many problems and many scales. This is really one of the first messages I want to give you. In particular, what I do is study regimes, like nano to micro, where fluctuations are very important. So it's important that the bigger, larger scale is also important. Instance ecology is also a larger scale. There are humans interacting with us, and there are ecosystems and things that are much bigger than a cell. Okay, so just to illustrate a bit, here are a couple of videos. Not going very fast, but this is a tracked bacteria. So here we have one of the statistics. The glass fiber is trying to move it to find food, and making some range of motion. Going very fast. But just to show you that thing. Cellular motion. Cellular motion. And particular. And look at these videos, and say there is something living alive here. And then this piece, I would like to know what makes this motion a signature of life, different to putting, for example, a grain of pollen water. Actually, this is one of the questions I've been asking. Here the videos don't work very well, but these are micro swimmers that look important, and they find here a crystal of sugar. So they can sense the sugar close by their hungry cluster to get energy and food. Okay. So another important example that we will see today this afternoon by the Catholics, for sure we will prepare a spectacular seminar, is the cell division. You can see here cell division. How we go to a biological book, you can see the cell division. You can see a cartoon. Cell genetic information chromosomes, the device into two, that are identical. Okay. Wow. This is here. Copying the cell. Now we can go from one to two. So you have to figure out, and look in this process, that apart from being quite nice, spectacularly perfect in some scenarios, you need to create a cell. From a cell to cells, you need something. You need resources. You need energy. This is something that was a bit under the carpet in biology. So I don't know this. I didn't study this so much. You know what happens? You know about DNA, how this process is possible. It's a rough idea. But now as we see this, we should say, how can we divide the cell into two? It's an open question. We as a piece of this, we can say a lot. Me as someone who studies thermodynamics, cannot divide someone something without giving it. Energy is what we call in thermodynamics, non-equilibrium. Not an equilibrium process. And of course, now it's much nicer. You can see television at the microscope. This is a real imaging, real-time video. Here below, it was said, Iwatovic lab. She will show these very nice movies where you see the chromosomes how they divide in real time. Again, size, quite microns. Not only you can do this, but you can also measure the forces that these chromosomes are pulling. And this is what brings the physicists to make these studies. They have to do both physics. Now I will keep myself in micro-scale as we said around microns. So I will repeat where are we. This is an example of the microscopic scale. I will try to divide, let's say the physical reality into three levels. One is the microscopic scale where we live. This is described by Newton's law. For example, this guy is in the yard. He hits force with a ball. And if you know these are conditions, where are the balls, the exact force is putting in the game, you will be able to predict the dynamics of these balls. This is called Newtonian-Terministic Dynamics, the macroscale. But if you look at the muscle of this person, the smaller small scales, you will find these fibres which are responsible for muscle contraction and using power. And here, the power is generated by very small tiny motors, machines that are like nanometers pulling all together fibres so that it can all together play the game. Nice way. The motion of a single of these machines, the motor, is extremely affected by noise. These are in a thermal environment. There are water molecules around or other molecules interacting with this motor. And the motor moves in a sort of stochastic or random way. It has a direction, but there are pathways. So here we cannot use classical mechanics. And there will be a lot of lectures talking about this stochastic lineup, Markov process, probability theory. So things are probabilistic. There is some randomness to this level. This is why I am very destined to start here. Resistance, you can even go smaller and smaller and look at one protein on the leg of the motor and this is the atomic scale. Well, again, you cannot use classical Newtonian dynamics. You cannot use stochastic dynamics, but you go to so small scales that you need to use quantum mechanics. So I said many scales, many tools from physics and I will mostly, today, discuss at this level, which is, for me, very interesting and fun. For instance, I am talking... By the way, if you have questions, please, you have me because this is for students, not a conference. Okay, so this is one of the fibers, the muscle, if you sum it, you will find... These structures are fibers, acting fibers, which are pulled by these other motor proteins, that's called mysics, that look like they're all together. We can bind and unbind the acting filaments and also pull. We are able to... Let me show it now. Here, this is something very traditional, hometown, ship, road, and they use energy to move. Both, in this case, these minus-in motors are here for growing, and this will be ship water. Generic power. Of course here, people who are growing, they need to put something in energy to produce work. It's not something that comes for free. If you don't have breakfast today, you cannot come here and row and fast and produce more things. And this is really happening, not for here. There is a source of energy. There are very energetic molecules that are attached to these myosin, and they take this molecule, which is literally called ATP. They break this molecule, and when the molecule is broken, it gives them a lot of energy. It gives them to... ...broke. So there are cycles. I think this appears in many books. Biology, biophysics, which happens in complicated dynamics that are simplified in a way. A very energetic molecule touches this motor, and then this molecule hydrolyzes. It breaks smaller molecules, and this generates energy that can be used by this motor to attach this filament and also to pull from the filament. Once this muscle is produced, these molecules are released, and the dynamics starts again. So then there is a cycle. Cycles are happening all the time in biology. Molecules are attached, detached, broken, and a type of energy here is chemistry, is converted into another type of energy. One thing is chemical components. Another thing is, if I take the bottle of water and they move, this is also changing the energy. I take it up here. Increase the potential energy of the water. Here is a conversion of energy. Chemical energy, chemical reactions, that is transforming to work. Mechanical energy used to move this body. This is, of course, an illustration. And again, I'm trying to be very deductive just to introduce you to different models. There are many. It's not the only one. This, for example, is called kinesi. This is a motor. This is an animation. The video should be this molecule. Motor protein. It's able to transport vesicles in the cell. For example, this would be a round spherical vesicle which has food, nutrients for the cell. And you may think, okay, when I eat molecules that are broken, they enter into vesicles, they enter the cell, and then they diffuse freely. Like if you put a small object in the sea, okay, this would be the case. It wouldn't be alive. We need things that are carried and moved fast, like post-office, send a letter because you need a machine that is capable of this. These machines are quite tiny and they can move incredibly big, much 10 or 30 times bigger than the motor. This is quite fascinating. We can't know ourselves. Without this, we couldn't have a transporant, efficient functioning of ourselves. This is a sensor for life. Not only things we use, but there are small machines that move things in highways, in trucks, in rails. This is done with small machines. I say here, I put a very sketchy sentence, I realize it, and I move. I mean that every time this machine does a step because it's using chemical energy. It takes this highly energetic molecule, breaks, gives a lot of energy to the motor, and then it can do a step. Things do not move by magic. It's just a conversion of chemical energy into mechanical work. Again, this is a classic movie. You can see it from the 90s, a long time ago. Every time the motor makes a step, there is a cycle. The motor has a touch, a molecule, the motor has broken, the motor has given energy to the motor. The motor makes a step, and then it releases. It's a molecule, adding fuel in every step. And then it starts again. There are cycles. We release energy. We call it free energy. A sensor for things you need. Molecules that are highly energetic. And again, this is to be didactic. I reiterate. This happens at small scales, nanometers. Just waiting. Just waiting for updates. Every step of the motor, as I said, the motor is nano, one step is nanometer, 10 to the minus 9 meters. The steps happen in very fast times, 10 to the minus 6 seconds. And, sorry, this motor particularly makes one step first. There are processes that happen 10 to the minus 6 seconds. We do mining. Chaining. Chaining is in the molecules. And the energy, as I said, for every step of the motor, one needs to burn a molecule. And the amount of energy that this molecule gives you is of the order of KBT. KBT is the Boltzmann constant times the temperature. It's the energy of what the molecule has. That's KBT. But this chemical reaction gives you more than KBT. If you're around 10 KBT, because it would be just one KBT of the energy of a water molecule, you won't be able to move. Because one single water molecule will drag you behind. You need something more energetic. Around 10 KBT, which is around 10 to the minus 21 units. To make one step, the motor uses a very small energy. Very small compared to us. Moving a small object for one meter, this will be one tool. This is 10 to the minus 21. These are the scales we are talking about. And these are two-side challenges. On one side, we would like to understand these motors. How they work. Why they move like this? How efficient they are. But on the second, we would like to take inspiration from this motion to be saying non-machines in the future. This is one of the key challenges of this century. You would like, for example, to take a drug and put it in a machine that goes to a specific organ and puts the drug in the place. It doesn't go through your body. And for this, we need non-machines. Small devices. Learning about biology. This scale is useful. It will be very useful in the future. Of course, a big time. Something very important is that when you look at these small scales, mesoscopic, big smooth, here is a small object. Loyal particle. This is the size of a cell. And if you put one of these objects, you can trap it with a laser trap. And you look at it in time. This is an experimental movie. It's not a computer game. This is a real experiment. You look at the particle, it moves in shakes in all directions. So it looks like a drug. Moving up, left, right, up, down, all the time. There are what we call fluctuations. This thing is fluctuating in time. And if you do an experiment and you measure the position of this particle as a function of time, you will see that it has this shaking motion. This is what we call fluctuating for stochastic motion. It's very different from the yarn. When the yarn is trajectory, how the ball moves will be straight line. This move. These scales, please, are not smooth. Have a microscope. Laser, I see where the particle is. Quite noisy. This is what we call fluctuation. Simple one. Position of this particle is fluctuation. So, in physics, who was the first to talk about fluctuation? So, study fluctuation comes back from Brown. Brown was not a physicist who was looking at pollen grains under the microscope. And you see here that he was looking at the pollen grains. A microscope, you could see. Very unfortunate and lucky with this projector, but this guy, the pollen grains in water also shake and move in a random fashion. So, it looks like that. Then how is it? It's not smooth. It's not deterministic. So, Brown is all this. It's happening here. Are they alive? The bacteria are showing you the beginning of the representation. It's alive. Why do they move? Why do they move like this? This straight line. So, took a long time to find the reasonable explanation. You can see here, this ball is following the center of mass of the particle. It has this type of particle. And key answer will give me my answer. Einstein was the person who said Brown's emotion particle is a manifestation of the terminology of molecules comprising particles in body. Einstein had the idea that this ball is moving in a radical because of the interaction of the particle with the environment. It's like you are in a crowded environment and you are a big guy. You are a very, very small guy and they are fast, very quick and they are hitting to you all the time. It's a simple idea. This is this before. I didn't even think there were atoms. How can you have this idea 100 years ago? Einstein was a big supporter of atomic theory. Nature, matter is made of atoms. You believe in atoms, in the atoms and the particle is nothing. It's quite nothing. Indeed, Einstein thought it was a theory or the mean square displacement of the particle. If you look at this particle for a long time and you do a trajectory, on average the same amount of time to the left and to the right. You will not drift. You are not pushing the ball. But if you put the particle and you wait a long time it starts to diffuse and move around. If you look at the square and position of the particle this means I do many experiments. I put the particle in center and I look at it for a second and I do it again and I do it again and I collect the x square after one second. This quantity which is called mean square displacement grows in nothing time. The more time you wait the bigger is the fusion. Where is the particle? It's shown experimentally but Einstein developed a theory which showed this is the fusion. This is a bit of the basis of biophysics. Identifying what is the physical model for the fusion. The fusion happens a lot. It's simple. Excuse me, if I could interrupt you. First component, as you mentioned Einstein may be one of the most interesting information. The first wife of Einstein was Serbia. Actually it is, I don't know is it correct somehow it is like the equations were written by Mila and I don't know is it like an opinion because she was of course of history. Did you say it too? Yeah. An act of pigment. You know when we got there Mila was the first Einstein from Serbia. It was one of the five female students at the age of two. And she was with one mathematician and I think that I was correct. But there was evidence that she really took five female students there was also very funny story Einstein and Marilyn Monroe when Marilyn Monroe told the Einstein role to imagine that who passed their baby and that the baby is viral and cute and nice looking as me. And Einstein answered yes but I'm concerned because he has to propose it. Why? One more reason for the interaction is that we are now at 12 or 2 and and I suppose to be connected so maybe we would need it is for it. If you want I can to see it I would like to hear the quote but it is also easier to check I can break it into parts. I don't have a problem. But maybe to see it is Andre there. I cannot. Mr. Yes I'm here I was just unable to unmute myself. Andre is I'm here can you hear me? We cannot hear him. You cannot hear me? Hello? Hi. Yeah we can hear you. You can only then in the okay they can hear me. You inside. Hi Can you hear me? Yes please. Andre so maybe it is a good idea if I can finish one part it will be soon. And then you could connect this is fine. That's fine. Can you hear me now? We will resolve the issue in the meantime but I hope the few said yes. Yes please. Okay that is okay. Okay so I will speak until the last 20 and then we can connect. Very good. Because what I'm going to say it is quite useful for the lecture of Andre which is very important historical and not by any means in the end. I just wanted to explain the concept that will appear for sure. It is that microscopic scale has a statistical nature so if you take this particle I'm telling you and you prepare the particle in X equal to 0 today put it there and you look at it you may see the motion of this particle in the X position back to 18 times it's way and if you do the same experiment one day later put also the particle in X equal to 0 you will see the motion following this red trajectory which is not exactly the same but if you prepare the same conditions this is because of the statistical nature of Brownian motion this is called stochastic process Stochastic process is a process given in this condition you can have a function of time different outcome different phenomenon and the stock market stock option time and tomorrow maybe it can start in the same position in the market then different outcome here it is very important to note that what does it mean to prepare a system in this case I see the particle I cannot only track the particle I don't see the molecules of the particle I have the particle there but the molecules of the particle I don't see them it's key in the stochastic process there are variables that I don't see there are many they are very quick so the motion of these water molecules is quick I cannot see but I do a model only for x and this model has noise the noise is used to model all the rest to be environmentally and of course I prepare my experiment in the same way because the particle is exactly the same place but the bath molecules typically are going to be in different places based on the experiment so this is an important remark but you will see in address motion use many of the talks you will see this type of phenomenon one dimension solution this is the dimension it will be motion it's not as a function of time but the molecule of the particle draws this trajectory x,y space this is the dimensions but if you have to read I have to I have to read how you extract the particle to help us to predict some how the stochastic process depends this is a this is a big challenge and this is a this is a task not only for biophysics but also for inferences so many techniques are going to you are going to I can explain tomorrow there are two classes of models that are widely used which I think André and also Rafael can also explain one class is called the fusion process or Langevin equations where you have the motion of fluid and there are different forces there is a force from a potential you can create a laser trap and then there is an extra force that we have and we call Gaussian white noise which models the impacts of all the rest of the model so we do a force balance equation in which one of the terms stochastic force is stochastic force which at all times the force takes another different value it's like drawing a random number it's okay if you don't know this about this model I am very happy to explain I can explain it tomorrow and typically this noise has some properties similar to Brownian motion it's a noise that is Gaussian it's taking from a Gaussian distribution it has zero mean it has zero mean and it has no memory there is a noise that does not remember it's called Gaussian white noise and it's used to model thermal factors you have an object in a thermal path it's in one class of models and another class of models is Langevin equations for things that move they can move in all the space there is another class of models which is described for example this cycle there is state A, state B and you have a model that our system is jumping this is called Markov Markov jump process and this André will explain because he is a big partner of this model which we use quite a lot so these are like two classes of models that are common in use one is Langevin equations and the other is called Markov jump process and both are connected but they are widely used and they are very accurate to describe this cycle I don't know with time for much but just to say that in looking at this projection we realize that we will not study the particle position but as a distribution here x goes to rho of x we look at these three bosoms because it has statistical nature I was at 0 I am still now at the later time I am in two different possible states so it is important to study what is the probability that I will end up here Mr. Casting process we keep the tool that we use is probability field and you are a good probability you know probability theory you could do and study in a very scientific way statistical physics is the basis in equilibrium thermodynamics and also biophysics and I think with time I just finished with this slide for Andre Camps and it is also motivating to his talk in physics there are red events so you can have again this column and you can make it move out of equilibrium so you can put a force field and it is pushing this particle in one direction there is an average tendency of the particle to go here but there are red events and the particle can also move backward against the force this is key Mr. Casting we see red events I am more interested in the red events than the typical myself as a my curiosity I would like to understand how lightning is to see a very extreme a thin flat region which is quite relevant and not only we see this in physics matter plastic particle or glass particle in living systems and I am trying to the presentation is living but it is not working I just wanted to tell you that if you look you track the position of a single moth I see it here sorry it is already bad but the connection ok so sorry ok in my second in my second in first first yeah same it was that is related yes it is image of a molecular moving here a couple of seconds it will be a sample of a logical system that also has really bad here is a sketch of experiment where you can track the motion of a motor step by step here step is a momentum very very tiny and you can see maximum time where is the motor along the field and you can see that it moves up every time every time it is up you need to step forward but sometimes it is a back step sometimes the motor is moving back even though it has energy to move forward to move forward a cargo or a bicycle in one direction so it really does happen and they are quite important to characterize the efficiency of this process so we end up here in the back to the top to show you biology at small scale and I hope I will continue with this topic and tomorrow I will continue with this so thanks thank you very much it was very very very good you like it? ok thanks thank you thank you for the presentation