Great advances have been made in recent years in terms of defining the biochemical basis of cell behavior as well as the biophysical properties of the individual cytoskeletal molecules that form the structural framework of the cell. Yet, little is known about how these individual molecules join together in space to form higher order cellular structures that can change shape, move and grow. We have presented a model of cytoskeletal structure and cell mechanics that is based on the concept that living cells use tensegrity architecture to control their shape and function. Studies with stick and string tensegrity cell models predict that living cells are hard-wired to respond immediately to external mechanical stresses. This hard-wiring exists in the form of discrete cytoskeletal filament networks that mechanically couple specific cell surface receptors, such as integrins, to nuclear matrix scaffolds and to signal transducing molecules that physically associate with the cytoskeleton. Experimental work from our lab has confirmed that many of the molecules that mediate signaling by growth factors and extracellular matrix are immobilized on the cytoskeleton and concentrated at the sites of integrin clustering in the focal adhesions that anchor the cells to their substrate. If these signaling molecules do function in a <solid-state=, then mechanical stresses may be transduced into biochemical responses through force-dependent changes in cytoskeletal geometry or structure. Changes in cytoskeletal tension (prestress) may also play a role in signal amplification and adaptation. Recent mechanical deformation in the regulation of cell growth, differentiation and apoptosis. I also will review studies which provide direct support for the tensegrity theory as well as a preliminary mathematical basis. This work raises the possibility that we may be able to fabricate synthetic <biomimetic= materials that exhibit the mechanical responsiveness and biochemical processing capabilities of living cells in the near future, a possibility we are beginning to explore through a collaboration with industry (Molecular Geodesics Inc.).
Pertinent References:
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2. Wang N, Butler JP, Ingber DE. 1993. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124-1127.
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4. Maniotis A, Chen C, Ingber DE. Demonstration of mechanical connections between integrins, cytoskeletal filaments and nucleoplasm that stabilize nuclear structure. Proc. Natl. Acad. Sci. USA 1997; 94:849-854.
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