Functional Biomembrane Architectures in Mesoporous Materials

非技术总结该项目的目标是将生物膜材料结合到介孔(5-50 nm孔径)凝胶材料中，用于发现新药、产生能量和有效地将药物输送到人体。生物膜作为生物的主力，承载着作为受体、通道、转运体和酶的蛋白质，只要蛋白质仍然嵌入生物膜宿主中，就能产生能量。同样，介孔无机和有机凝胶和玻璃是现代技术的主力，具有独特的孔隙率、光化学、光学和催化性能。在这个项目中，通过将生物膜和膜蛋白的性质与介孔凝胶材料的独特性质相结合，将产生改良的生物材料。这些新生物材料的性质将通过挑战生物物理和材料表征来研究，从未研究的生物有机/无机界面的科学角度以及想象和优化任何未来的应用都是重要的。拟议的活动将为工程学学生提供生物技术和生物材料方面的培训，招收不同的研究生和本科生，通过组织国际研讨会进行思想交流，并通过研讨会和指导教学经验吸引大一和本科生的工程师。这项建议的目标是实施一种新的方法，将完整的膜蛋白(IMP)包裹到二氧化硅和二氧化钛基介孔溶胶-凝胶中，以制备和研究更好的材料，这种材料结合了功能完整的膜蛋白的性质(受体-配体相互作用和离子泵浦)和溶胶-凝胶材料的独特性质(分别高孔率和光催化)。这些复合介孔生物材料的原位表征将被用来研究溶胶-凝胶化学和纳米限制细节对IMP结构、功能、动力学和环境的影响。这项提案的另一个目标将是利用在开发pH和拥挤触发的膜结构方面的发现和经验来设计和研究介孔二氧化硅纳米颗粒(MSN)作为药物输送载体的内腔室逃逸策略。所提出的策略提供了表征和研究介孔表面对膜和相关蛋白质的动力学和热力学行为的影响以及研究内体逃逸的分子机制的机会。为实现这些目标而工作的工程学本科生和研究生将在生产功能生物复合材料溶胶-凝胶衍生材料的背景下，接受新的细胞生物和基因工程技术(即无细胞表达)方面的有价值的跨学科培训。这个项目将包括组织一个国际研讨会，创建一个通过研究食物来介绍生物材料概念的新生研讨会，指导一个本科生团队做一个筛选平台，以及指导工程学本科生的教学经验。这个奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.