Biomechanical Regulation of Cellular Signaling and Organization

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"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."There is a growing body of literature suggesting that cells use mechanical forces to transmit information and guide the assembly of multi-cellular structures. For example, during development, wound healing, and the creation of engineered tissues, cells exert mechanical forces that remodel their local environment by reorganizing the extracellular matrix (ECM) and result in cellular motion and organization. The research objective of this award is to couple experiments and computational simulations to develop a quantitative understanding of how cells use mechanical forces to signal and organize. Experimental studies will focus on observing the motion of cells and their surrounding extracellular matrix in several in vitro models of tissue morphogesesis. With these data, image-based finite element models and cellular automaton simulations will be used to determine the relative contribution of differential adhesion and stress propagation through ECM in the formation of multi-cellular structures. The formation of multi-cellular structures is essential in all except the simplest life forms. If successful, the results of this research will provide an improved understanding of the role of mechanical forces in this important process. The specific model systems studied in this work (i.e., islet-like cell clusters and microvascular networks) are closed related to efforts to engineer a number of tissues, including islets for type-I diabetics. The broader impact of our multi-disciplinary approach to integrating experiment with computations in mechanobiology research will present new opportunities to explore innovative undergraduate- and graduate-level educational initiatives within the newly-formed Department of Biomedical Engineering at OSU. In addition, high school students participating in the ongoing summer programs at the Ohio Supercomputing Center will be introduced to computational simulations using hands-on activities based on models developed as part of the proposed research.