Functional Biomembrane Architectures in Mesoporous Materials

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NON-TECHNICAL SUMMARYThe goal of this project is to incorporate biological membrane materials into mesoporous (5-50 nm pores) gel materials to be used for discovery of new medicines, energy generation, and efficient delivery of medicine to the body. Biological membranes serve as biological workhorses by hosting proteins that serve as receptors, channels, transporters, enzymes, and produce energy as long as the proteins remain embedded in biological membrane hosts. Similarly, mesoporous inorganic and organic gels and glasses are workhorses of modern technology yielding unique porosity, photochemical, optical, and catalytic properties. In this project, improved biomaterials will be produced by combining the properties of biological membranes and membrane proteins with the unique properties of mesoporous gel materials. The properties of these new biomaterials will be studied by challenging biophysical and materials characterization, important from a scientific standpoint of unstudied biological organic/inorganic interfaces as well as toward imagining and optimizing any future applications. The proposed activities will provide engineering students with training in biotechnology and biomaterials, recruit a diverse pool of graduate and undergraduate students, provide for exchange of ideas at an international level by organization of an international workshop, and engage freshman and undergraduate engineers via seminars and mentored teaching experiences.TECHNICAL SUMMARY A goal of this proposal will be to implement a novel approach to encapsulate integral membrane proteins (IMPs) into silica- and titania-based mesoporous sol-gels in order to make and study better materials that combine the properties of functional integral membrane proteins (receptor-ligand interactions and ion pumping) with the unique properties of sol-gel materials (high porosity and photocatalysis, respectively). Characterization of these composite mesoporous biomaterials by in-situ methods will be used to study the influence of sol-gel chemistry and nano-confinement details on IMP structure, function, dynamics, and environment. Another goal of this proposal will be to leverage findings and experience in developing pH and crowding-triggered membrane architectures to engineer and study endosomal compartment escape strategies for mesoporous silica nanoparticles (MSNs) as drug delivery vehicles. The proposed strategies provide opportunities to characterize and study the influence of a mesoporous surface on the dynamic and thermodynamic behavior of a membrane and associated proteins and examine the molecular mechanism of endosomal escape. Engineering undergraduates and graduate students working toward these goals will receive valuable interdisciplinary training in new cell biological and genetic engineering techniques, i.e. cell free expression, in the context of production of functional biocomposite sol-gel derived materials. This project will involve organization of an international workshop, creation of a freshman seminar that introduces concepts of biomaterials through study of food, mentoring of an undergraduate team to make a screening platform, and mentored teaching experiences for engineering undergraduates.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.