Modeling of Endothelial Cell Adhesion Dynamics Modulated by Experimental Molecular Engineering

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This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).In experimental biomechanical studies, a common problem is the difficulty of conducting a large number of tests for the efficacy time course of engineering manipulation. An integrated experimental and computational molecular biomechanics model for the enhancement of endothelial cell adhesion in arterial reconstruction is proposed. Endothelial cells play a critical role for protecting blood vessels against thrombosis and atherosclerosis, which is associated with platelet activation and blood coagulation. Endothelial cell lining of arterial constructs is an effective approach for preventing intimal hyperplasia in reconstructed arteries. However, endothelial cells often detach from reconstructed arteries due to weak adhesion strength, hampering the effectiveness of endothelial cell lining. Hence, the research thrusts are: (1) the adhesion of endothelial cells will be enhanced by experimental molecular modulation of selected adhesion regulatory factors; (2) the focal contact association/dissociation rates of the intergrin receptor and ligand pair binding at the molecular level will be computed; and (3) the adhesion strength of modulated endothelial cells will be predicted by computational simulation under various hemodynamic conditions. Societal Impact and Intellectual Merit: Vascular thrombosis, intimal hyperplasia, and atherosclerosis are common disorders affecting about 50% of the human population. Thus, a novel investigation leading to a potential reduction in these disorders will elicit significant impact in the scientific as well as non-scientific communities. The proposed research, while using the arterial reconstruction model as an example, addresses a fundamental topic: enhancing a desired cell function by modulating molecular activities, a potentially effective engineering approach not only for basic scientific research but also for the treatment of pathological disorders. Although this investigation focuses on endothelial cell adhesion in arterial reconstruction, the concept of integrating computational approach with experimental molecular modulation of cell function can be generalized and used for other pathological disorders.