Collaborative Research: Molecular Mechanics Dictate the Mechanical Behavior of an Extracellular Matrix Fiber

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The objective of the research is to characterize the mechanical properties of the fibrillar form of fibronectin, and extracellular matrix structure that is essential for development and that is upregulated in pathologies such as cancer and atherosclerosis, through the analysis of a model system of fibronectin fibers and the use of a computational model built upon the stochastic properties of fibronectin molecules. Fibronectin is assembled into a unique material in vivo with extreme extensibility, leading to speculation that its litany of binding sites for cells and cell signaling molecules may be actuated by mechanical force. This proposal is unique in that it will quantify physical properties of fibronectin fibers that define its function in vivo over a wide range of mechanical strains and attempt to connect these physical properties with the molecular architecture of the fiber. The approach will utilize a technique for quantifying the molecular structure of fibronectin molecules in model fibers that will be compared with a computational model of fibronectin fiber mechanical properties that considers both molecular unfolding and entropic spring-like behavior of fibronectin molecules.By combining all of these efforts, we expect this interdisciplinary proposal not only to generate a fundamental understanding of the underlying mechanisms governing mechanotransduction but also to have broad ranging implications in regenerative medicine and tissue engineering due to the fundamental role of fibronectin in vivo. It is surprising that despite our vast understanding of the importance of the physical environment on the behavior of virtually every studied cell, relatively little is known about the properties of native extracellular matrix structures. This program will be transformative in its capacity to promote new approaches in mechanotransduction research, as well as to immerse undergraduate and graduate students in a broad range of technological innovation. Active participation of both women and minority students will be fostered via a collaborative relationship with the Society of Women Engineers and Minority Engineers Society. Furthermore, this project will serve as a vehicle for the development of lab modules for courses at Boston University and Cornell University that are targeted for 3rd year undergraduate students.