CAREER: Physical Regulation of Cell Migration by the Glycocalyx

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This Faculty Early Career Development Program (CAREER) project will investigate how cells migrate in narrow spaces. All cells are coated in a sugar-rich coating of long molecules called a glycocalyx. The glycocalyx changes dramatically in many lethal diseases, but little is known about how changes in this cell coating make a disease better or worse. This project will create new tools for precision engineering of the mechanical properties of the glycocalyx. They will be used to determine the role of glycocalyx in cell migration. Cell migration is crucial in how many diseases progress. For example, the results of the project could lead to new approaches to preventing the spread of metastatic cancer cells. The tools for glycocalyx engineering are expected to be applied broadly in biotechnology to generate protective and anti-adhesive coatings on cells for diverse applications, including cell-based therapies and cellular production systems for bio-manufacturing. Therefore, results from this research will be important beyond basic research. The project will also include a comprehensive education and outreach program that introduces middle and high school students to physical biology with the goal of increasing participation of economically disadvantaged and other under-represented groups in science, technology, engineering, and math (STEM) subjectsPhysical forces generated by and acting on cells directly influence tissue homeostasis and progression to disease states. Recent studies emphasize that cells can migrate independent of integrins in 3D environments, where the glycocalyx is believed to provide traction against the extracellular matrix (ECM) for propulsion. Despite the growing appreciation for the role of the glycocalyx in cell migration and mechanotransduction, our overall physical understanding of the structure and its precise mechanisms of action in cell motility remain primitive. The research will address this challenge through development of a new toolkit for precision engineering of the glycocalyx and application of the toolkit, along with nanoscale imaging approaches, to understand the physical function of the glycocalyx in cell migration. The research will test the specific hypothesis that the glycocalyx provides physical cues that direct acquisition of specific migration phenotypes in confined 3D environments. The tools and fundamental knowledge developed will be broadly relevant in understanding the function of the glycocalyx in normal physiology and disease-specific contexts.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.