Periodic Reporting for period 3 - LubSat (Unravelling Multi-scale Oral Lubrication Mechanisms (macro-to-nano): A Novel Strategy to Target Satiety)
Période du rapport: 2020-11-01 au 2022-04-30
Obesity is a serious form of malnutrition that is known to have substantial morbidity and mortality consequences. For the first time in human history, the obese (body mass index, BMI ≥30 kg/m2) and overweight (BMI of 25–<30 kg/m2) population has surpassed the underweight. Medical treatment of obesity is currently limited to bariatric surgery which carries significant post-operative risks, and even after the surgery, sustained weight loss can only be achieved through well-designed nutritional interventions. Hence, 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, the changing dynamics of food properties in the oral mucosa remains the greatest source of uncertainty when designing food structure. In particular, our quantitative understanding of food-saliva interactions 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. This is in part related to the erroneous use of mechanical engineering devices manufactured with steel, glass and hard polymeric surfaces to measure food tribological i.e. lubrication and friction properties that do not emulate the textured surface of bio-tribo contact surfaces (i.e. the soft, micro-papillated human tongue and the hard upper palate). Oral lubrication, which can significantly affect psychological and physiological consequences of appetite suppression implicated in enhanced or reduced hedonic perception, altered salivary flow with more or less lubricating mucin content, changed motivation to eat and satiety (i.e. impact on appetitive ratings, food intake and hormonal biomarkers), 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
The key achievements of the project so far are the 1) development of oro-surface mimicked tribological devices at macroscale, 2) fundamental understanding of the salivary lubrication mechanisms at multiple length scales, as planned, 3) design of microgels with high lubrication performance
We successfully developed a highly innovative oro-tribometer surface that emulates the deformability, textured surface and wettability of real human tongue. In order to achieve this, we first understood the features present in real human tongue by taking masks of human tongue in healthy volunteers. In addition, we analyzed the wettability, deformability and geometric features of pig’s tongue (postmortem). 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 tribolohical 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.
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 remains as a mystery to date. As hypothesized in the plan, 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. Our discovery evidenced by multi-scale investigation of the properties of the binary model versus real human saliva, covering 9 orders of magnitudes of applied force, from 1 nN to 1 N 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.
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. This is expected to allow designing fat mimetics in food that can give pleasurable mouthfeel without adding any high calorie fat to the formulation.
We successfully developed a highly innovative oro-tribometer surface that emulates the deformability, textured surface and wettability of real human tongue. In order to achieve this, we first understood the features present in real human tongue by taking masks of human tongue in healthy volunteers. In addition, we analyzed the wettability, deformability and geometric features of pig’s tongue (postmortem). 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 tribolohical 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.
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 remains as a mystery to date. As hypothesized in the plan, 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. Our discovery evidenced by multi-scale investigation of the properties of the binary model versus real human saliva, covering 9 orders of magnitudes of applied force, from 1 nN to 1 N 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.
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. This is expected to allow designing fat mimetics in food that can give pleasurable mouthfeel without adding any high calorie fat to the formulation.
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 generated in this project will open new horizons for engineering bio-mimetic salivary substitutes for patients suffering from Xerostomia (dry mouth). (2) The oro-tribology tools developed will offer new ways of quantitatively measuring lubrication in biological systems, serving as a diagnostic tool for objectively assessing Xerostomia. (3) The realistic biomimetic emulation of the tongue surface and its properties will open up exciting possibilities for developers to perform high-throughput objective screenings of newly designed products. It will replace significant proportions of human sensory studies that are time-consuming, expensive and prone to large variations, and therefore greatly accelerate the product development cycle of food, oral care, oral medicine sector. (4) The innovative structuring of biocompatible microgel will have applications in personal care, pharmaceutical for oral and cutaneous applications. The biocompatible lubricious microgelled structures might also find applications for creating commercial high performance lubricants for surgical procedures such as insertion/ removal of endoscopes, catheters and other inserts.