 I'm going to talk about, yeah, it's titled over here, Structural Biology of Stimulary Responsive Namasellulose Interfaces. That is work that we have done over the past, I would say maybe eight to 10 years. And it is framed a little bit in the motivation to give some answers, some ideas how to fight global obesity. This is a map that is updating, and you see how the work is getting bigger. And the idea of tackling that problem, of course, there are multiple of them. We have tried a lot. Most of the stuff is of the ideas are not really working simply because we are not forcing ourselves to really adhere to the rules. So the general idea is that one has to, or that we try to reduce overweight and obesity. And there's a lot of ideas, as mentioned before, we have ruled out fat as ingredients that is creating overweight and obesity. We have, we came up with artificial sweetness. And then of course also we have the discussion on fibers and fullness. And more recently, people are talking about interaction with mucus and biofilms in the small intestine. And what I would like to come up, or what I would like to discuss over here is actually playing around with the lipid digestion and the lipid uptake. Basically, we're thinking a little bit the role of fat. And that was introduced 10 years ago by Matt Golding and Tim Booster at that time at CSIRO in Melbourne. Basically saying that when we have fat in our food, we actually also are able to, our body is able to induce satiety hormones that are going to stop eating. The problem is that we take our fat, it is digested in the stomach and then it's more than in the small intestine. So the problem over here is more that we have to get the fat to the right place. And this concept is put together in the concept of the iron grate. So that once the lipid is reaching the small intestine, we have the triggering of these satiety hormones. So that is of course happening normally at the end of the meal. We would actually like to do that at the beginning of the meal. So having actually fat going there, not digested. And that is now the problem that we have that basically it will be digested in the stomach and that goes already pre-digested in the small intestine. So it's really just not working when we have the first bite of fat that we are eating. And the idea is now to generate lipid emergence that are going to survive the stomach. So that is an idea that was put up 10 years ago. We followed that a bit and we teamed up actually also with people from the university hospital next door. And when you're going to hear some emergency vehicle coming arriving over here, it's just simply because my office is just next to the emergency room. So the idea was then carried on, as I said, with people from the university hospital in Zurich. And these are images of different emulsions and actually the gastric content volume wise when feeding or when putting people in an MRI device. And what you see over here in the white areas, this is basically the stomach. It is filled with a fatty solution and emulsion system and it's back down and depending on the structure, one has different gastric volume over time. So that is monitored over two hours, three hours. And we see that actually the structure is very much changing over this time and actually also those, the emptying of the stomach. So here we have already an indication that we have a control on the food. Digestion, the stability of the emulsion, controlled by the stability of the emulsion. Good, so that was a little bit of the framing and indication that by designing food, we have a direct influence on, for example, the gastric volume, the emptying of the stomach. Now the problem is how to make these these emulsion systems so that they're stable in the gastric environment, but they're breaking down in the intestine environment. And what we have to consider here is the different pHs, the mechanical stresses that we have in the stomach, even though I'm not going to talk about that. We have mucus in both stomach and intestine. We have changes of joint extension, of course, also temperature is body temperature. So from the food that we take, maybe at 20 degrees or whatever, it is going to be heating up to 37 degrees when we don't have fever. And so these are a lot of boundary conditions to basically have these emulsion stable. And what I'm going to discuss a little bit in the following are actually four steps that we made to go from not only the design of the emulsion, where we actually looked also a little bit more deeper in neutron activity measurements, but we also would like to understand how these emulsion is then stable in vitro environment. And then, of course, also, if the entire idea is actually working in vivo. So here at the very end, I will also present you some experimental data that we have obtained from humans and from rats. Okay, how to make these emulsion? Or let's say the interface of these emulsion. Well, classically, a lot of food emulsions are stabilized by proteins. This is a summary of the adsorption of proteins, conformational changes to network building of a gel or more glassy interface that is stabilizing the emulsion. There's a lot of work on that. I always like to refer to the PhD thesis of Benjamin's from Wageningen University, who really nicely put that together some 20 years ago. But there's a lot of extensive work on that area existing. The other system that became a little bit more popular over the last, I would say, 10 years, as you see also here with the citations are particles. And when you look into literature, there's actually a whole bunch of particles that have been investigated. So starch, flavonoid crystals or particles, ketene, zinc, and in particular, cellulose, and or cellulose nanocrystals. I'm going to stick with the cellulose nanocrystals for the rest of my talk as we, in the beginning of the project, actually screened the others, but found that the cellulose nanocrystals are most probably the most potent candidate for stabilizing the emulsion, in particular when mixing them with proteins, as we will see later. There's a lot of work done in that area over the last 10 years. And I just mentioned to a few articles that are both very recent, that are putting these work together. So the first one is from the Leeds Group, Sakha and Dickinson. And then later on, we also had a review on that. But I also like to mention that others like Kalashnikov I also have written nice overviews on the last 10 years of this research. Good. So what we now looked into a little bit more in detail is that we used crystalline nanocellulose and modified them in different ways. So what we see over here, so this is all work that we have done over the last years, we used unmodified cellulose, we methylated them or esterified them. And the unmodified one is relatively less surface active. So here you do see changes in the adsorption basically by the addition of the salt. With the methylated one in the middle, we see that methylation actually increases the adsorption of the particles at the interface, increasing the surface pressure. And with the esterified material, it's a little bit more tricky because they really just have to spread by solvent and will, as we see later on, build a relatively patchy layer. But that is the zoo of the cellulose particles that we used and we, I mean, modified them in different ways. So basically playing around with the hydrophobicity of the material and looked into their adsorption, their rheology and their structure. And for the first, a very brief introduction to the method that we use for the interfacial rheology. So this is the bicone setup that we have developed some years ago where we basically measure elasticity, viscosity, viscosity of these adsorption layer between oil and water or just between water and air. With all these cables that you see or tubings that you see on the left-hand side, we are changing the environmental conditions. So this is basically our little stomach or intestine that we are using. So here we can change pH, we can add life paces and increase temperature to see what is going to happen with these layers when we are going to physiologic conditions. And one example over here is beta-lactyl globulin. So a protein that we adsorb at the interface between oil and water. So we see G-prime, G-double-primes or elastic and storage modulus as function of time. And we did a lot of now steps that are sort of linked to the two digestion. So we heated up to 37 degrees, we used the pH and then we added pepsin. So you see for all these steps actually the interfacial layer structure is always becoming lesser and weaker in signal. And eventually after a few hours completely is destroyed. So that is something that we actually don't want in this situation, that the emulsion is actually broken and digested already in gastric conditions. So here we're not going to bring these emulsions into the small intestine. And now a little bit closer look to the methylated non-acrystalline cellulose that we have used. So you have here again the plot of the surface pressure as function of different methylation steps. And you see that with increasing methylation the cellulose goes to the interface and reduces surface tension or increases actually surface pressure. Material is normally a few nanometers with and the length is about 10 times of that. So we have work like aggregates that are now sitting at the interface establishing a layer there. And what is also important to see is or actually a benefit for us is that these methylated celluloses they do a thermal dilation normally embark that it is it's around at 50 degrees Celsius at interfaces it's far lower. So it's 22 degrees. And what we see here is when we increase the temperature we see that G prime, G double prime is also increasing. So here we have a thermal dilation that actually also helps us to stabilize the emulsion with a layer of celluloses around. And when we look to the right I think we have over here shows to prime G double prime for the different methylation steps. And we see that these thermal dilation is helping us a lot in particular for the material that has the highest methylation steps. So we start the three, four and five at the very end on the very right end of the graph. So this is a benefit that we have certainly when trying to stabilize the emulsions. And now I'm just showing you the same experiment that we have done now with the methylated cellulose and the better like the globulin together under gusted conditions. So it's the same experiment that we've done with the better globulin alone. But what you see over here is that in every step that we do accept maybe the addition or the change of the pH the layer is actually getting stronger. So we add the methylated cellulose. It builds up the layer that is a composite layer with a better like the globulin temperature increase induces a thermal dilation and the addition of pepsin. So gastric environment is actually not changing things at all. So here we have a nice proof that or at least from the interfacial biology that the material is really resistance against the gastric environment. So the emulsion stays intact. And now let's turn a little bit to the neutron reflectivity measurements that we have done for these materials. So what you see over here is well the normal reflectivity curve as function of the scattering vector. And we don't have too much features over here. So the curves are relatively flat which we actually all see for protein systems at least food protein systems throughout the way. But what we are going to see is that with the thermal dilation actually also the layer structure is changing. And with, I mean, playing around with fitting we basically can come up with a model on the right hand side so that we have a 22 degrees Celsius. Some of the material sitting at the interface approximately 13 angstrom thick but relatively diffuse layer penetrating into the bark. And when we are now going to the higher temperatures so 70, 30, 70 degrees we have a more compact layer that is thicker about 150 angstroms of thickness. So here we already see the thermal dilation is kicking in and helping us to build a layer structure that is protecting the interface. Now in the next step or in the next graph over here we put together the experiments with the different ingredients that we have. So here we are talking or we have actually the pure water-air interface. We have the better lacto-globulin layer. We have the pure methylated and the crystallized cellulose. Then with better lacto-globulin together and in the final state actually also the compressed one. And depending from the reflectivity curves so the upper right we again calculated scattering density and basically came up with the cartoon in the middle where we have the better lacto-globulin layer about 20 angstroms, methylated cellulose 120, 150 and then the composite layer, the same thickness. So we have indication that the better lacto-globulin is really used is the cement between the cellulose and we can even by compressing not really changing that structure too much. Okay. So that is a little bit of the situation for the methylated cellulose. So this is actually the cartoon over here in the middle. And I also would like to show you the two other materials that we have used the modified and the esterified material and try to give a little bit of a summary what we have observed them. So maybe for the starting with the unmodified material here, we see a relatively slow adsorption. So it really takes hours and that is most probably also the reason why there are sometimes indications in the literature that it does not observe. Actually it does, but you really have to wait hours. You can increase the adsorption by salt. So that is something that tremendously pushes the particles to the interface. But actually it's a relatively discontinuous layer and the coverage is very small. So basically for the idea that we had, it's not appropriate. The middle one, the methylated one as discussed before is a monolayer that we can with a thermal dilation push into a multi-layer structure actually also with the metal lacto-globulin as a composite, then being relatively stable or actually very stable, fugastic environment. You would see that in a few slides down the road. The last one, the esterified ones is we always can spread that with solvent so they didn't absorb from the bark due to the hydrophobicity. And here we have a system that actually has a relatively high contact angle. And as a result, we see actually a system that is more aggregated and building clusters. Interesting, and here again, same system, but now microscopy images. So for the unmodified, you see actually nice distribution but still it's not really a continuous layer. Methylated, a more dense one and the esterified, the clustered one. I mean, in the lower row, we see actually the rheology signal of the material and I really would like to point out to the lower right one for the esterified one. Here we see a Maxwell kind of behavior of the adsorption layer and I think that is one of the very few examples where that is going to happen. So normally it is just a gel structure that we observe for these kind of materials that interfaces and most probably due to the contact angle and we have the situation that the material is behaving as a Maxwell figure. But that is more a little bit of a side note. Okay, and now the question, does that stuff really helps us to survive with a droplet in the gastric environment and the intestine environment? So what we have done here in the first step are in vitro studies, we used lipases, we also used mucus and we looked into the structuring of the food during the digestion. So that was done with a marginal system that was MCT, so medium chain triglyceride at water systems and we also used recombinant top gastric lipases for this experiment. So the first experiment is actually microfluidics one. So we made our emulsion and we kept the emulsion droplets covered with cellulose and beta ducted globulin in little traps as you see in the picture on the right hand side over here. And then we were changing from the generation mode, making the droplet to the digestion mode and we added now different first gastric and then pancreatic lipases to digest the droplets in the trap. And what you see in the lower row is basically a field trap on the left hand side then coalescence the digestion of the droplets and then eventually to the far right disappearing of the oil droplets. So here then the digestion would be over. A little more in a transient way, actually you can see these with now two videos. The first one on the left hand side is starting. So it shows the droplet in one trap. You have the gastric environment when nothing is happening and then in the pancreatic environment the droplet is disappearing. So simply saying that in the gastric environment it survives and once we switched to the pancreatic environment it doesn't. The next movie is more or less doing the same thing. So we have the gastric environment, nothing is really happening. And then in the pancreatic environment is actually the droplet is breaking down rapidly not only having coalescence, just showing the movies again right now in parallel. So you see gastric nothing is happening at least minor things maybe coalescence and pancreatic does dissolve. The pictures put together here in the graph. So you see in the gastric environment relatively small changes of droplet diameter we have a few coalescence effects over here. So that means that the diameter is becoming larger but once we go into the pancreatic environment within let's say 15 minutes or even less the droplet are all digested. So basically the achievement that we survived the stomach and have the release of the fat in the small intestine is given. And now last thing for the last few minutes is does it work with humans and with rats? And so for that we went back as mentioned before to the University Hospital running MRI signals. And what you see here on the left hand side is stomach so the white circled with a yellow circle or circle fence there. So the white material or the white image is the fat emulsion, black is air. And now with the data processing we actually can also say what is fat and what is water. So the blue one is water. And you see that the fat layer is red on top of the of the emulsion sorry of the stomach and content over here and black again is air. So that is a whole bunch of calculation and procedure. I'm not going to look into that into detail actually also and not really my competence over here. What we have now is in the end these figures. So this is actually the stomach of the first author of the paper that is down there. And she was drinking these three emulsion systems and one stabilized with beta-lactoglobulin methylated cellulose and nanocrystalline cellulose. And what we now can nicely see when we scan through the with the MRE through the stomach that we have for the beta-lactoglobulin decreeming. So here the emulsion is breaking up it is digested with the methylated cellulose we have a dilution effect and with the nanocrystalline cellulose we have a structuring. So here the situation with the beta-lactoglobulin basically is the solution of the emulsion. So we have a digestion going on and for the two others we don't. And we have then now modern monitor that actually also with the gastrointestinal responses. So we look into triglycerides in blood, plasma CCK and the gallbladder volume. And what you see here is a very rapid response to the wave protein isolate. So beta-lactoglobulin simply saying well the emulsion is breaking down. We have uptake of fat, triglycerides are going up, satiety signal is coming up as well very rapidly. When we go to the methylated cellulose it is all delayed and flattened. So basically what we would like to have to see when we go even to these very high methylated nanocrystalline cellulose the signal is almost not there. So that means that here we don't sense any of the material. So it is so stable that it is even not digested in these timeframe that we have. So that basically also says well with monitoring, manipulating the interfacial structure of the emulsion we really can trigger different gastrointestinal responses. So hormone releases fatty acids in the blood and the method I think we can conclude it's showing that with the structuring we can really monitor and control the takeout. Last picture is with accumulated food intake with rats. So you cannot do that with humans feeding them for two days or even more with these emulsions. So we have done that with rats and you see that with the way protein stabilized food intake basically they're eating constantly with the nanocrystalline cellulose, the black one they are eating but then they're not changing or eating more after the two hours or three hours while with methylated cellulose we have lesser food intake compared to the two others but it's actually also relatively rapidly at the beginning and then stays constant. So here again the two cellulose systems basically show in a different way. I mean for individually differently that food intake can be actually controlled by the interfacial structure. Okay, and with that I'm going to finish. So what we, I hope that what I could show you is that by designing interfacial layers with different materials in particular here with proteins and celluloses one can generate emulsions that are differently behaving towards both in vitro and in vivo gastric and interstellar environment and by that helping to structure firstly the food emulsion that we have and by that also controlling their digestion and the lipid take up eventually in the small intestine. And yeah, I think with that I'm going to finish and thank you for your attention. Thank you Peter, it was a very nice talk. I'm sure all my colleagues enjoyed it as well and we have a few questions. So I'm going to start by asking Lawrence, we have a few minutes so I can actually ask the person to ask the question live. Lawrence, are you? Yeah, yes. Can you hear me? Yes. Yeah, Peter, nice talk. It was just a curiosity. You showed that there was a huge difference in gelation temperature at the interface and in the bulk and I was wondering whether you know where it comes from? Yeah, well, I mean the methylated cellulose is gelling at higher temperature. That's an effect that you basically exclude fluid volume in the environment of the cellulose. And I mean that is working in bulk and I think as we are constraining the system to more or less 2D by the adsorption we have less, let's say free space available and then it actually kicks in earlier. So it needs less temperature increase to do so but that is really speculation. I mean we never, I mean went into that into full detail it's, yeah a little bit, I think that the problem when you go from 3D to 2D that some of them, yeah let's say environmental conditions are changing. So the same thing with, I mean, actually also the viology response that we almost just see less, I mean gel-like or rubber-like behavior but never behavior like a Maxwell fluid. So yeah, okay. Thank you. Tommy also has a question on the reflectance data. So Tommy, when I asked the reflectance data question. So Peter in the first curve that you show on the neutron reflectivity on the cellulose layer it seems it implies that there are two layers. There is a kink in the SLD profile. Sorry to be very detailed but. Yeah, no problem. So do you think that the layer next to the surface is denser or different than from the more extented layer because it seems that there is a difference in there. This is, so that, that one. Well, I mean, you mean this one over here or the- No, that was wrong. Okay, let's see one more up. That one over here. No, I think that was, that's the better like the other one, that one, yeah. That worked one way. It implies to me that there is a, because you see like a plateau layer and then there is something wide distribution. I mean, that is, well, you know that better than me. I mean, getting a final structure out of these needs a little bit of art and imagination. And we basically came up with this conclusion over the drawing in using also these AFM images that we have. And so the layer structure at the top, I think as you said is indeed a little bit denser than when you go into the, closer to the bulk. So, and you know, playing around with these parts and fitting, I mean, you can basically shift around I mean density and layer thickness and roughness. I think still there is always a little bit of interpretation left and maybe other ways to say, but we know or we always do these or did that fitting also having the AFM images in mind. And that's the way to do it, I think. Maybe another contrast also could have. Yeah, yeah, yeah. Okay. There's a question from Kirsten. Kirsten, would you like to ask it? Yeah, this is a little off another track, but I was thinking about if these emulsions can be sort of too stable for a quality in the perception and the sensory but this is two things that I have to say over there. The MCT oil that we used in the first experiments, it was sort of a very creamy emulsion. So you cannot drink too much of those then you throw up so that basically says how tasty they are. And the situation with the MCC with the methylated nanocrystalline cellulose, there the emulsion is so stable that you basically just eat a filler. So it's almost, I mean, eventually yes, but I mean, it's almost impossible to penetrate that layer in given time. Of course, we haven't considered any motion and mixing in the stomach. So from that point, maybe it's also different. But I mean, coming back to your question, from the sensory, the stuff is all not nice. And the idea initially or let's say how we actually yeah, we're thinking of using the material is sort of in form of a salad dressing or something that is not a drink that you where you drink 200 milliliters before starting eating or something like that because then I think the meal is spoiled. So we basically have to camouflage that emulsion system in a way that people are still drinking it. And that is really a big problem. Thank you, Peter. There is also a question related to microfluidics and how you did the in situ digestion work. And actually I'm gonna expand it a little bit and we have only one minute left before the next speaker. But if, what happens between the gastric and the intestinal? Do you wash the digested material out or everything stays there? And Tommy's asking also if you had bile salts in the system. I mean, all these experiments, they were done as closely as possible. And I think a big difference to most of the in vitro studies is that we kept the digested, I mean, we wash out the digested material in the gastric situation, but not too much is happening. So everything is still left but structured by the gastric environment before we are going into the pancreatic environment. So it's really not that we do two different steps we do as it is going to happen in real one after the other. So that, and that actually also shows that the pre-structuring that we have of the very stable emulsion in the stomach is has an enormous impact on the pancreatic digestion. So it would be certainly differently when we expose the emulsions individually first to the, or parallel to the gastric and then to the intestine situation. So it's really in one after the other like it happens in vivo. Yeah. Okay, well, thank you, Peter.