Functional Biomembrane Architectures in Mesoporous Materials

该项目的目标是将生物膜材料结合到介孔（5-50纳米孔）凝胶材料中，用于新药的发现、能源的产生和药物的有效输送到体内。生物膜作为生物的主力军，承载着作为受体、通道、转运体、酶和产生能量的蛋白质，只要这些蛋白质仍然嵌入生物膜宿主中。同样，介孔无机和有机凝胶和玻璃是现代技术的主力，具有独特的孔隙度、光化学、光学和催化性能。在本项目中，将生物膜和膜蛋白的特性与介孔凝胶材料的独特特性相结合，生产改进的生物材料。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，从尚未研究的生物有机/无机界面的科学角度来看，这对于想象和优化任何未来的应用都很重要。拟议的活动将为工程专业学生提供生物技术和生物材料方面的培训，招募多样化的研究生和本科生，通过组织国际研讨会提供国际层面的思想交流，并通过研讨会和指导教学经验吸引新生和本科生工程师。本提案的目标是实现一种将整体膜蛋白（imp）封装到二氧化硅和二氧化钛基介孔溶胶-凝胶中的新方法，以便制造和研究更好的材料，将功能整体膜蛋白的特性（受体-配体相互作用和离子泵送）与溶胶-凝胶材料的独特特性（分别为高孔隙率和光催化）结合起来。通过原位方法表征这些复合介孔生物材料将用于研究溶胶-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。本提案的另一个目标将是利用在开发pH值和拥挤触发膜结构方面的发现和经验来设计和研究作为药物递送载体的介孔二氧化硅纳米颗粒（MSNs）的内体室逃逸策略。所提出的策略为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检查内体逃逸的分子机制提供了机会。朝着这些目标努力的工程本科生和研究生将在新的细胞生物学和基因工程技术方面接受有价值的跨学科培训，即细胞自由表达，在生产功能性生物复合溶胶-凝胶衍生材料的背景下。该项目将包括组织一个国际研讨会，创建一个新生研讨会，通过研究食物来介绍生物材料的概念，指导一个本科生团队制作筛选平台，以及指导工程本科生的教学经验。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.