Modulation of Macro and Micro Mechanics of ECM by DDR1

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The research objective of this award is to use a combination of biophysical and computational tools to investigate the mechanics of the extracellular matrix (ECM) and how it is modified by proteins secreted by the cells. The ECM in most vertebrate tissue is composed primarily of collagen type 1 fibers. The structure of collagen fibers can be modulated by a number of collagen binding proteins. The proposed studies will evaluate the effect of such ultra-structural modifications in collagen fibers on the mechanical properties of the 3D matrix and on cell-matrix interactions at the macro and micro-scale levels using optical tweezers, uniaxial testing and gel contraction. In parallel, a multi-scale computational model will be developed to model the global and local mechanical responses of the collagen fiber matrix to uniaxial stress and traction forces exerted by the cells. If successful, these studies will provide novel insights into how naturally-induced alterations in the collagen ultra-structure can affect matrix mechanics, cell-matrix interaction and mechano-transduction. These results will impact the biophysics, biomechanics, biomaterials, and tissue engineering communities. The proposed activities will also develop novel methodologies for experimental and computational studies of the ECM. The educational plan will train two PhD-level graduate students with a diverse set of knowledge and hands-on skills in cell and matrix biology, microscopy, mechanical testing, instrument design, modeling and simulation, thus preparing them to meet the upcoming scientific challenges and tackle complex problems at the interface of engineering and biology. A new workshop on biomechanics is planned for middle school girls.