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

水凝胶在生物学中代表了一类未被研究的分子组合，有许多有趣而重要的结构-功能问题有待发现，工程应用有待发明。核孔，例如核膜中的微小通道，被一种水凝胶填充，这种水凝胶控制着细胞核和细胞质之间的选择性分子交换。另一种重要的生物凝胶是粘液，由多肽和糖亚单位组合而成的高度水合的生物聚合物制成。粘液覆盖在人体所有潮湿的表面，提供了一种选择性屏障，允许营养物质和信息进入，同时将病原体拒之门外。水凝胶是生物学不可分割的一部分，然而，关于它们如何发挥作用的明确概念尚不清楚。该项目的目标是阐明生物凝胶作为选择性屏障和过滤器的基本生物物理原理，以及构建和调节它们的细胞机制。该项目还将教育和吸引社区卫生领导人、教师和学生了解水凝胶的最新科学，强调粘液屏障在自然生物材料物理学的更广泛背景下的重要性。这项研究也将成为开发免费在线教材的基石，包括一本儿童书籍和一场视频比赛，使公众能够广泛了解生物水凝胶。核孔过滤器是阐明水凝胶生物过滤一般原理的理想系统。它的分子组成具有很好的特性，也可以由定义明确的富含苯丙氨酸的重复单元重组。将使用一套独特的定量方法和理论工具来表征选择性运输，并阐明粒子的生化特性与其跨越核孔水凝胶屏障的移动性之间的关系。该项目还将设计水凝胶过滤器，精确控制屏障的选定元素，包括重复单元的大小、电荷和交联化学。PI的目的是通过解决重复结构域在调节屏障选择性中的作用，大幅扩展现有的水凝胶过滤研究技术，并将该领域推向新的前沿。重复结构域是许多生物凝胶的基本构件。她的目标是为一个理论框架提供基础，该框架捕捉到控制核孔选择性的一般原则，可能还包括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.