CAREER: SELECTIVE TRANSPORT IN BIOLOGICAL HYDROGELS - FROM DESIGN PRINCIPLES TO MECHANISMS

在生物学中，水凝胶代表了一类尚未被充分研究的分子组合，有许多引人入胜和重要的结构-功能问题有待发现，并有许多工程应用有待发明。例如，核孔，即核膜上的微小通道，充满了水凝胶，水凝胶控制着细胞核和细胞质之间分子的选择性交换。另一种重要的生物凝胶是粘液，由多肽和糖亚基结合而成的高度水合的生物聚合物制成。粘液覆盖了人体所有潮湿的表面，提供了一个选择性屏障，允许营养物质和信息进入，同时阻止病原体进入。水凝胶是生物学不可分割的一部分，然而，关于它们如何起作用的明确概念却缺失了。该项目的目标是阐明允许生物凝胶作为选择性屏障和过滤器的基本生物物理原理，以及参与构建和调节它们的细胞机制。该项目还将教育社区卫生领袖、教师和学生，让他们了解最先进的水凝胶科学，强调黏液屏障在更广泛的自然生物材料物理学背景下的重要性。这项研究还将成为开发免费在线教学材料的基石，包括一本儿童书籍和一个视频比赛，使公众广泛认识和理解生物水凝胶。核孔过滤器是阐明水凝胶生物过滤一般原理的理想系统。它的分子组成有很好的表征，也可以由定义明确的富苯丙氨酸重复单元重构。一套独特的定量方法和理论工具将用于表征选择性运输，并阐明粒子的生化特性与其通过核孔水凝胶屏障的迁移率之间的关系。该项目还将设计水凝胶过滤器，精确控制屏障的选定元素，包括大小、电荷和重复单元的交联化学。PI的目标是通过解决重复结构域（许多生物凝胶的基本构建块）在屏障选择性调节中的功能，实质性地扩展现有技术来研究基于水凝胶的过滤，并将该领域推进到新的前沿。她的目标是为一个理论框架提供基础，该框架可以捕捉控制核孔选择性的一般原理，也可能适用于其他重要的生物水凝胶，如粘液和细菌生物膜。

Hydrogels in Biology represent a class of molecular assemblies that are understudied, with many fascinating and important structure-function problems to discover and engineering applications to invent. Nuclear pores, for example, the tiny channels in the nuclear envelope, are filled with a hydrogel that controls the selective exchange of molecules between the nucleus and the cytoplasm. Another important biogel is mucus, made from highly hydrated biopolymers from a ombination of peptide and sugar subunits. Mucus coats all the wet surfaces in the human body, providing a selective barrier that allows nutrients and information in while keeping pathogens out. Hydrogels are an integral part of Biology and, yet, clear concepts of how they function are missing. The goal of this project is to elucidate the fundamental biophysical principles that allow biogels to act as selective barriers and filters, and the cellular mechanisms involved in building and regulating them. The project also will educate and engage community health leaders, teachers and students about the state-of-the-art science of hydrogels, emphasizing the importance of mucus barriers within the broader context of the Physics of nature's bio-materials. The research will also be the cornerstone for the development of free online teaching material, including a children's book and a video contest, enabling widespread public awareness and understanding of biological hydrogels. The nuclear pore filter is an ideal system in which to elucidate general principles of biofiltration by hydrogels. Its molecular composition is well characterized, and can also be reconstituted from well-defined phenylalanine-rich repeat units. A unique suite of quantitativ methods and theoretical tools will be used to characterize selective transport and to elucidate the relationship between a particle's biochemical properties, and its mobility across nuclear pore hydrogel barriers. The project will also engineer hydrogel filters with a precise control of selected elements of the barrier, including the size, the charge, and the cross-link chemistry of the repeat units. The PI's aim is to substantially extend the already existing technology to study hydrogelbased filtering, and advance the field toward new frontiers, by addressing the function of repeat domains, the basic building blocks of many biological gels, in the regulation of barrier selectivity. Her goal is to provide the foundation for a theoretical framework that captures general principles governing selectivity in the nuclear pore, and likely also in other important biological hydrogels such as the mucus, and bacterial biofilms.