CAREER: Synthetic mucus gels with tunable glycosylation, composition, and physical properties

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Project Non-Technical AbstractWith this award, the Biomaterials Program in the Division of Materials Research is funding Dr. Jessica R. Kramer from The University of Utah to develop polymers to mimic natural human mucus. Mucus is essential for life but remains challenging to study due to a lack of access to reproducible and homogeneous samples. This award funds development of new methods to synthesize the protein component of mucus and to study how these proteins interact with each other and with salts, DNA, and bacteria to form mucus. These materials have broad implications for probing interactions at cell-surfaces such as nutrient absorption, fertilization, and immunity and could be used in cellular models to reduce the need for animal testing. This pursuit allows undergraduate and graduate students to acquire specialized training in polymer science, microbiology, and glycobiology. This project also integrates into several outreach programs that support glycoscience education and females in the pursuit of STEM careers, and targets students from 4th grade to the graduate level. Project Technical AbstractThis research project undertakes development of a multi-block self-assembling glycopolypeptides that mimic the properties of multi-domain mucin glycoproteins. Mucins are the major protein component of mucus hydrogels that coat epithelial tissues, and are essential for life. Yet, mucins remain challenging to study due to a lack of tools to analyze and manipulate protein glycoforms. Lack of reproducible access to sufficient quantities of homogeneous mucins has hindered research in many areas of science and medicine. Mucin-mimicking multi-domain polypeptides with precise glycosylation patterns and tunable domain are chemically synthesized by sequential polymerization of amino acid N-carboxyanhydrides. The glycopolypeptides are assembled into hydrogels containing varied compositions of salts, lipids, and DNA to investigate factors responsible for mucus' bulk physical properties. The contributions of glycan-binding bacteria and galectins to the stiffness or degradation of mucus will also be explored. Overall, this study provides new materials for the study of mucus at the molecular level. This research also integrates into several outreach programs that support glycoscience education and females in the pursuit of STEM careers, and targets students from 4th grade to the graduate level.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.