Tissue engineering is a relatively new but rapidly expanding field of biomedical engineering research. Because cell adhesion and motility are two critical factors in determining tissue integrity and function, elucidation and regulation of the cellular and molecular mechanisms involved in cell adhesion and motility is fundamentally important for tissue engineering. Implementation of engineered tissues in clinical applications has been successful in soft-tissue replacement or regeneration. The general use of artificial tissues is limited, however. Detailed understanding of mechanisms regulating cell adhesion and motility is expected to provide insights for controlled cell seeding, improved designing and engineering of artificial tissues. Use of non-invasive electrical stimulation (ES) offers a novel non-mechanical technique to regulate cell adhesion and motility. Projects involving the use of ES in fibroblasts, hepatocytes, and white cells and studies of lateral and rotational dynamics of membrane proteins provided an excellent basis for the proposed hypotheses in this proposal. In response to ES, the mechanotransducer integrin is likely to mediate cell adhesion and motility. Integrins redistribute on the cell surface, interact with cytoskeleton, and actively participate in dynamic formation of focal adhesion contacts. Optimized use of ES has been shown to redistribute integrins, reorganize cytoskeleton, alter calcium homeostasis, and induce guided cell migration without adversely affecting cell viability. This proposal uses unique non-invasive optical techniques, including single particle tracking and laser optical trap, to 1) track, at the single molecule level, changes in integrin motion induced by ES on the surface of human fibroblasts; 2) measure changes in the strength of integrin-cytoskeleton interactions induced by ES on controlled 2 dimensional extracellular matrices; and 3) characterize electromechanically induced and integrin-dependent cell motility in reconstituted 3 dimensional gel model. The long-term objectives of the proposed research are to manipulate and control cell adhesion and motility by the optimal use of ES and, thereby, to enhance tissue integrity and function of engineered tissues.
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