University of Virginia Health System

Living cells and tissues adapt to their environment by altering structure, gene and protein expression, and biochemical functions. For example, endothelial cells lining the artery wall at the blood tissue interface experience fluid mechanical forces that vary with time and location along the artery. However, the mechanisms by which cells transduce mechanical stimuli into biochemical signals are not well understood. Our laboratory employs a multidisciplinary biomedical engineering approach to understand the relationship between intracellular mechanics and cell function.

Several tools are used for investigating cellular mechanotransduction. Expression of green fluorescent protein (GFP) fused to cytoskeletal or other proteins makes it possible to visualize endogenous intracellular structures, and fluorescence probes enable detection of intracellular signaling molecules such as nitric oxide. High-resolution optical sectioning microscopy, deconvolution, and 3-D image restoration provide quantitative spatial and temporal information. Quantitative image analysis tools analyze intracellular movement, molecular interactions, and biochemical response. Nanotechnology-based structures control mechanical stimuli at the length scale of individual protein structures near the cell surface. Engineering nanoscale spatial cues into the cell’s local environment will enable rational design of cell phenotype for regenerative medicine and tissue engineering. Thus, projects in our laboratory bring together a joint biomedical engineering, materials science, and molecular biology approach to understanding cellular physiology.

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