CAREER: Peptide stereocomplexes as dynamic junctions in polymeric biomaterials

点击翻译按钮获取中文摘要

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).Non-technical Abstract:Developing materials that mimic the mechanical, chemical, and biological properties of natural tissue is important for advancing national health infrastructure. Such materials support the growth and delivery of therapeutic cells for repair of damaged tissue and enable researchers to study disease progression for identification and evaluation of new treatment approaches. Research in chemistry, materials science, biology, and engineering has produced a range of tunable tissue-mimicking materials and associated fabrication methods. While these biomaterials capture various aspects of native tissue, there remain compelling opportunities to improve both the production processes and materials properties to comprehensively capture the complex, highly functional features of native tissue in an accessible, scalable manner. This project will employ advanced synthetic and characterization techniques to develop new ways to prepare and tune the properties of water-swollen, tissue-mimetic materials composed of synthetic polymers and protein fragments called peptides. To inspire and guide a diverse cohort of students towards rewarding careers at the forefront of biomaterials research and education, this project involves the design, implementation, and dissemination of structured early-stage undergraduate research and educational experiences. Technical Abstract:To advance the ability of biomaterials to recapitulate the complex, highly functional characteristics of native tissue, it is important to develop ways to tune materials properties in an accessible, scalable manner. The goal of this project is to invoke stereochemistry-driven interactions to advance the manufacturing, control, and function of next-generation biomaterials. Stereochemistry-driven complexation, or ‘stereocomplexation’ of macromolecules produces marked changes in stability and thermomechanical properties of materials, yet there is limited understanding about the molecular features driving stereocomplexation and how complex strength impacts the properties of stereocomplexed materials. Since peptide synthesis enables routine generation of peptides with exquisite control of sequence and stereochemistry, peptides with complementary stereochemistry provide an ideal materials platform for answering these questions. The objectives of this project are to (1) determine how peptide molecular features (e.g., length, charge, and hydrophobicity) impact stereocomplexation; and (2) connect molecular-scale features of peptide stereocomplexes to the bulk properties (e.g., stiffness, viscoelasticity, and stability) of polymeric hydrogels cross-linked with peptide stereocomplexes. Establishing design rules for peptide stereocomplexation and determining the roles of these dynamic complexes in modulating biomaterials properties represent critical steps to advancing stereochemistry as a design parameter to control materials properties. Complementing and enriching the research objectives, educational objectives include structuring the early stages of undergraduate research to recruit and provide engaging experiences that empower a diverse group of biomaterials researchers. A research-based course series bridging multiple institutions will guide students in building core competencies and networks to propel their future careers.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.