OK hi everybody Mamie's parents for a oppose doc in Princeton and I'm going to tell you about basically two stories today one is how that contract and said this in The Express or the Matrix interact mechanically where there is there and violent and how that affects the stiffness of the surround and the second store so that's basically relating experiments to maybe make or break does that mean grow and a fantastic buzz document and. I'm just doing the theory so I'm just going to tell you about whatever where they've done the second part of the story is about how we have been using with Martin Lance and chase borders using this data to infer stress fields in these three D. expect that our matrix. So consider this contract and cell here it's a cancer cell but really what it's been selected for is just because it is under surrounding collection matrix so question is the most abundant protein in your body it's it's there in cattle agent tendons It's what gives us to two to delist it into your skin. And it's well known to have a strong one in their mechanical properties and what the them and they just have been doing is that they've put small beads small latex beads inside this matrix and actively pulled on it using optical tweezers and then they've been measuring the skills of force against displacement and far from the cell you get is that curve which has starts pretty pretty stuffed and then stiffens when you get either you when you go to stronger forces so it's not in the early stiffening just as you would expect from macroscopic which when you get closer to the cell along the contraction axis you see that this curve gets steeper and steeper and you actually get a stiffer mechanical response to these micro probes. So. This is generic Actually it's not specific to could I Jen But if you do it's two in favor of a more complex networked called could make major gel you in all these cases you get strong stiffening near the said contraction axis of up to two or the magnitude of stiffening and that stiffening range is about once a length in size which is pretty long relished. And by doing a lot of clever controls what they found is that really what induces the stiffening is the contract and properties of the Center For instance if you prevent them from for contracting the network relaxes and it becomes homogeneous soft. And so the first take home message is that the contract and sense really stiffen messily and in the extended range does their excessive matrix so what will they feel basically what they did where they feel when the pulling around is not to the nastiness of the Matrix it's really the stiffness that induce themselves because of this this stress and that's something that's been predicted there it equally unmeasured experimentally and so face to face measurement in the past but it's the first time that someone has shown it in three D. expects that I matrix. Now I've been telling you that it's stress that is responsible for this how can we does that how can we measure of stress in this in this is that we're all so it's a complicated problem and there are many challenges to measuring stresses in three D. These ordered none in the are that are yours at the local skate do one of these is the best approach on the markets it's called three D. direction force microscope and it's basically uses the difference that it measures strains by imaging before and after contraction and to do we have the better yield and assumes that. We know that as soon as that the micro mechanics is the same as the macro mechanics and then you can reconstruct some of the. Stress field but it's extremely hard to treat and in there it is it's it's basically ignored this order and it's. It's a it's really hard to apply. When I think I would like to propose is to develop a new method in which we use the known in narrative to measure stresses the way this works is that well you can measure this reference curve in which in which it's the derivative of the force displacement killed here including the differential stiffness as a function of the folks and it's in the locus of this in that that too is still in our regime it's still a nasty business and it increases with increasing force that's the only nasty thing that I've told you about before. Getting close to the close to the cell you get to that don't becomes higher and higher and it's because of the increasing stress that is responsible for an increase of the nastiness and so this it does that's interesting there's increasing step stress and increasing force we don't know about stress we don't have access to it but we know what the force because it is so our idea is to use force as a proxy to measure stresses so take a linear look at point in the point in your in your material you can measure the linear stiffness and its associated to an unknown stress you can you can read out the effective force that you would need to apply and stress to matter you are to get to the same Look at stiffness so this effective force F. F. effective is defined as the force you would need to apply to get the same stiffness as you get in at the in our order from the space so this is kind of a force. Stress correspondence and what you would like to say is OK for some stressed kind of similar quantities maybe they're proportional and it's it turns out that this is actually not such a simple. Solution No not so simple as as this first because force and stress have a difference to me trees forces a dunce or a forces effect of stresses at themselves and if you reverse the force you basically have a symmetry still there in the first if the stiffness is what I think in the force when the linear stiffness. Has got to have it in that in the stress because it's a there's no symmetry between one side stresses of uncompressed of stresses. What I've shown is that if you go too strongly in one in the order in a matter you'll that stiffens as a power load then actually you have the proportionality between these two terms which we called non-industrial which which is a correspondence between force and stress and allows us to infer stress. Using the measurement of the effective force and we called this technique known in a stress inference microscope. Just a small simulation to give you a kind of proof of called of principle. I've been using the same kind of networks as charming presented this morning that this time in three D. and there is none in the elements but it must it's here to mimic to do experiments so we have a contract and said here and this all these beads showed the stress field and that I measured numerically direct and now I'm going to infer the pull of these bones on into the stress using the stress of the technique that I just described and this is what I get so in the old these areas actually do there's no stress and the network is softer than planned that then the lid then the background stiffness so you can't infer stresses using this method but in all the parts where there's strong contraction. You get. A very faithful representation of the stress field. To a professor of the weather so I've responded to so so that a bit difficult but it's really a perfect of this project that we can get using the. Micro to calibrate our our of our technique so it's actually if you want this is a manual fights them and that is to use this technique. What you should do to infer. To infer stress fields in the media is first you get the micro you. Know didn't differential stiffness against force. And the macro. Stress the strain. Then you measure the stress feel. So this is the stress as a function of its weight then you measure the stiffness field this is the sickness as a function of the distance to the cell for instance and then you use the stiffness fields and and the dictionary between stiffness and effective force to read out the effective force and then you and this gives you the difficult stress and to check if your consistently applying the method you need to get you need to get. In there stiffness that is significant it consists. Larger than the background stiffness of the stress material you need to be in the strong in the one in which you are. Using this method we've been measuring stress fins in this system and what we've observed is that the. The stress is significantly larger than previously reported it was in the hundreds of us scales and interestingly it decays as it was inexplicable it made us do with this but distance to the to the cell and this menace to is actually something that was predicted. A number of groups including where my Ph D. work and that's something I think that's expected in such networks because of a few individual filaments in the network so that's that was the conclusion I was very proud of there's a smaller bet here because actually this is not a conclusive proof of this kind of network physics because the renge of this this is actually close to the tip of the said here so if it didn't minus three the two the gets from the now order is not valid. You need to think it about it as a two for some of the boards instead of a four as they pull and close to a force of the pull you get or sort of minus two which is the same prediction and there's a that they're not known in our. Predictions So that's kind of a confused confusion between what the political unknown in Advocate here that makes this to claim it to be and conclusive about long range FOS transmission but in any case we have long range stiffening in this network just to summarize we've shown that make you reveal this strong stiffening of the aesthetic. Of the United States matrix surrounding says we've developed stress in France method to. To infer stress is using this in Asked if this is and we've shown that the if we can measure stresses this way and with that this has been published last week in T.N.A. Yes And with that I'd like to thank you for your attention.