Periodic Reporting for period 4 - LubSat (Unravelling Multi-scale Oral Lubrication Mechanisms (macro-to-nano): A Novel Strategy to Target Satiety)
Okres sprawozdawczy: 2022-05-01 do 2023-10-31
Obesity is a serious form of malnutrition that is known to have substantial morbidity and mortality consequences. To directly promote weight management, there is an immense need for designing satiety-enhancing foods that terminate appetite for longer periods after consumption. It is now well-evidenced that satiety is enhanced when food is consumed orally rather than by gastro-intestinal infusion, where the former can be controlled only by food design aspects. However, our quantitative understanding of food-saliva interactions in the oral phase is very poor, yet of first-order importance for designing satiety-enhancing foods. To date, in-mouth lubrication properties of food have not been a part of meal design principles because of the lack of suitable quantitative techniques for measuring oral friction and lubrication. Oral lubrication, which can significantly affect psychological and physiological consequences of appetite suppression is poorly quantified and thus remains as a key barrier to design of satiety promoting foods.
Thus, the overarching goal of Project LubSat is thus to create a fundamental understanding of molecular interactions on the tribological, surface and structural properties of mouth-food biomolecules mixtures to establish bottom up principles with a vision to design satiety-targeted foods and there are two broad aims:
• Aim 1. Establish food biomolecule-saliva lubrication mechanisms at various length scales (macro-to-nano scale)
• Aim 2. Alter salivary lubricity with bottom-up designed food structure(s) to impact satiety
Thus, the overarching goal of Project LubSat is thus to create a fundamental understanding of molecular interactions on the tribological, surface and structural properties of mouth-food biomolecules mixtures to establish bottom up principles with a vision to design satiety-targeted foods and there are two broad aims:
• Aim 1. Establish food biomolecule-saliva lubrication mechanisms at various length scales (macro-to-nano scale)
• Aim 2. Alter salivary lubricity with bottom-up designed food structure(s) to impact satiety
In LubSat, we:
1) Developed the first ever oro-surface-mimicked tribometers with unprecedented surface topologies over the full macro-to-nano scale range of forces simulating the full tongue surface and surface of a single papillae.
2) Created new fundamental understanding of human salivary lubricity using in vitro and ex vivo approaches.
3) Designed super-lubricating, soft, prous, protein and starch "microgel" based food structures.
4) Demonstrated short-term oro-sensory satiety can be altered using mouth coating as a construct for the first time.
Key achievements of LubSat are:
1. Multiscale Oro-tribometers. We successfully developed a highly innovative oro-tribometer surface that emulates the deformability, textured surface and wettability of real human tongue. Using appropriate metrics taken from the human and pig’s tongue, we designed the first-ever biomimetic tongue-like surface using silicone materials with appropriate softness, wettability and surface roughness with precise texture using 3D-printing and soft lithographic techniques. The breakthrough was that this oro-tribometer surface not only replicated the architecture of real human tongue but also closely resembled the mechanoreception mesaured in terms of collision probablity as wel as experimentally measured tribological performance of a real human tongue mask. Thus, this new oro-tribometer surface serves as the first bio-mimicked tongue surface that can be used to measure the lubrication properties of food, saliva and orally administered fluids accurately. We also developed single tongue papillae like soft probe in an atomic force microscopy set up to measure lubricity at nanoscale where adhesion matters significantly. Both these ro-tribometers allowed discovering lubrication performance of proteins, polysachharides and also phase changing food structure such as chocolate.
2. Salivary lubrication deals with one of the most intricate examples of tribology in nature, where an adsorbed layer of saliva provides precisely controlled lubrication in the hardest (enamel) to one of the soft surfaces (tongue and oral mucosa) in the human physiology. However, the molecular mechanism behind this remarkable lubrication properties remained as a long standing mystery.We reported for the first time that a “binary model” comprised of purified salivary proteins (mucin and lactoferrin), forming an electrostatically driven, multi-layered assembly explains the true lubrication mechanism of human saliva at multiple length scales. Covering 9 orders of magnitudes of applied forces, from 1 nN to 1 N, we revealed that mucin controls the viscous lubrication that traps water within its mesh-like network, while the non-mucinous lactoferrin acts as a ‘molecular glue’ between mucin-mucin allowing water entrapment in the mucinous mesh as well as tethering mucin to the surface, latter aiding boundary lubrication. This study puts forwards an unprecedented model that is able to explain the synergistic lubrication of human salivary components.
3. Novel microgels containing 90-95% water and starch/ proteins were fabricated with unique processing techniques and were evidenced to show high lubricating performance when sheared in oral mimicking soft tribo-contact surfaces. Such lubrication properties were found to be dependent on the stiffness of the microgels, their volume fraction, the wettability of the surface, the type and viscosity of the continnum. We have created fat mimetics in food that can give pleasurable mouthfeel without adding any high calorie fat to the formulation. Formulations also created using plant proteins show exceptional hydration property and impart lubricity and excellent mouthfeel to otherwise "dry", "astringent" plant proteins.
4. Finally, using a combination of in vitro and in vivo (healthy human) trials, we have demonstrated for the first time that lubricity in the form of oral coating is an impotant factor in controlling appetite and food intake in short term in protein and/or polysaccharide containing food strucures. Such short-term influence in appetite ratings may have implications in designing satiety-enhancing snacking foods.
Exploitation and Disseminaton: This project has resulted in numerous peer-reviewed publications, patents, journal covers and media coverage.
1) Developed the first ever oro-surface-mimicked tribometers with unprecedented surface topologies over the full macro-to-nano scale range of forces simulating the full tongue surface and surface of a single papillae.
2) Created new fundamental understanding of human salivary lubricity using in vitro and ex vivo approaches.
3) Designed super-lubricating, soft, prous, protein and starch "microgel" based food structures.
4) Demonstrated short-term oro-sensory satiety can be altered using mouth coating as a construct for the first time.
Key achievements of LubSat are:
1. Multiscale Oro-tribometers. We successfully developed a highly innovative oro-tribometer surface that emulates the deformability, textured surface and wettability of real human tongue. Using appropriate metrics taken from the human and pig’s tongue, we designed the first-ever biomimetic tongue-like surface using silicone materials with appropriate softness, wettability and surface roughness with precise texture using 3D-printing and soft lithographic techniques. The breakthrough was that this oro-tribometer surface not only replicated the architecture of real human tongue but also closely resembled the mechanoreception mesaured in terms of collision probablity as wel as experimentally measured tribological performance of a real human tongue mask. Thus, this new oro-tribometer surface serves as the first bio-mimicked tongue surface that can be used to measure the lubrication properties of food, saliva and orally administered fluids accurately. We also developed single tongue papillae like soft probe in an atomic force microscopy set up to measure lubricity at nanoscale where adhesion matters significantly. Both these ro-tribometers allowed discovering lubrication performance of proteins, polysachharides and also phase changing food structure such as chocolate.
2. Salivary lubrication deals with one of the most intricate examples of tribology in nature, where an adsorbed layer of saliva provides precisely controlled lubrication in the hardest (enamel) to one of the soft surfaces (tongue and oral mucosa) in the human physiology. However, the molecular mechanism behind this remarkable lubrication properties remained as a long standing mystery.We reported for the first time that a “binary model” comprised of purified salivary proteins (mucin and lactoferrin), forming an electrostatically driven, multi-layered assembly explains the true lubrication mechanism of human saliva at multiple length scales. Covering 9 orders of magnitudes of applied forces, from 1 nN to 1 N, we revealed that mucin controls the viscous lubrication that traps water within its mesh-like network, while the non-mucinous lactoferrin acts as a ‘molecular glue’ between mucin-mucin allowing water entrapment in the mucinous mesh as well as tethering mucin to the surface, latter aiding boundary lubrication. This study puts forwards an unprecedented model that is able to explain the synergistic lubrication of human salivary components.
3. Novel microgels containing 90-95% water and starch/ proteins were fabricated with unique processing techniques and were evidenced to show high lubricating performance when sheared in oral mimicking soft tribo-contact surfaces. Such lubrication properties were found to be dependent on the stiffness of the microgels, their volume fraction, the wettability of the surface, the type and viscosity of the continnum. We have created fat mimetics in food that can give pleasurable mouthfeel without adding any high calorie fat to the formulation. Formulations also created using plant proteins show exceptional hydration property and impart lubricity and excellent mouthfeel to otherwise "dry", "astringent" plant proteins.
4. Finally, using a combination of in vitro and in vivo (healthy human) trials, we have demonstrated for the first time that lubricity in the form of oral coating is an impotant factor in controlling appetite and food intake in short term in protein and/or polysaccharide containing food strucures. Such short-term influence in appetite ratings may have implications in designing satiety-enhancing snacking foods.
Exploitation and Disseminaton: This project has resulted in numerous peer-reviewed publications, patents, journal covers and media coverage.
The project findings are expected to provide various technological platforms that, we believe, are very useful for a broader range of scientific disciplines such as soft matter sciences, synthetic biology, materials engineering, surface science. Some possible applications include: (1) Understanding of salivary lubrication and microgel-reinforced hydrogels generated in this project with outstanding lubrication performance will open new horizons for engineering bio-mimetic salivary substitutes for patients suffering from Xerostomia (dry mouth) with extended relief period providing long-term hydration. (2) The oro-tribology tools at macro and nanoscale developed will open up exciting possibilities for developers to perform high-throughput objective screenings of newly designed orally relevanr products. It will replace significant proportions of early human sensory studies that are time-consuming, expensive and prone to large variations, and therefore greatly accelerate the product development time cycle of food, oral care, oral medicinal applictaions. (4) The innovative structuring of biocompatible lubricious microgelled structures might also find applications for designing sustainable plant based foods for supporting planetary health and creating commercial high performance aqueous lubricants for biomedical applications such as for such as dry eyes, surgical procedures (e.g. insertion/ removal of endoscopes, catheters and other inserts).