Selective Transport in Biological Hydrogels -- From Design Principles to Mechanisms

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.