The mechanochemical basis of cell and tissue regulation.

This article is a summary of a lecture pre- sented at a symposium on "Mechanics and Chemistry of Biosystems" in honor of Professor Y.C. Fung that con- vened at the University of California, Irvine in Febru- ary 2004. The article reviews work from our laboratory that focuses on the mechanism by which mechanical and chemical signals interplay to control how individual cells decide whether to grow, differentiate, move, or die, and thereby promote pattern formation during tissue morpho- genesis. Pursuit of this challenge has required devel- opment and application of new microtechnologies, the- oretical formulations, computational models and bioin- formatics tools. These approaches have been used to ap- ply controlled mechanical stresses to specific cell surface molecules and to measure mechanical and biochemical responses; to control cell shape independently of chem- ical factors; and to handle the structural, hierarchical and informational complexity of living cells. Results of these studies have changed our view of how cells and tis- sues control their shape and mechanical properties, and have led to the discovery that integrins and the cytoskele- ton play a central role in cellular mechanotransduction. Recognition of these critical links between mechanics and cellular biochemistry should lead to novel strategies for the development of new drugs and engineered tissues, as well as biomimetic microdevices and nanotechnolo- gies that more effectively function within the context of living tissues. keyword: Mechanotransduction, integrins, cytoskele- ton, tensegrity, cell engineering, morphogenesis