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Dynamics of Cell Orientation

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Abstract Book of the XXIII IUPAP International Conference on Statistical Physics, Genova, Italy, (9-13 July 2007)

Abstract

Many physiological processes, such as bone and muscle growth, wound healing, and angiogenesis depend on the response of cells to mechanical forces; these can be generated either by the contractile activity of the cell or by external stresses. Understanding the response of cells embedded in gel matrices to mechanical loading is important not only for basic biological science but also for the rational design of artificial tissues 1. In recent years, it has been established that cells can actively sense the mechanical properties of their environment and respond in various ways. By pulling on their environment, cells actively sense rigidity gradients, boundaries and applied strains. Cells respond to these signals by actively adjusting their contractile forces, migratory activity, and orientations. A ubiquitous and puzzling experimental observation is that cells respond differently when the matrix is subjected to static strain compared with dynamically varying strain. For static strain, cells align parallel to the direction of applied strain 2 while for cyclic strain, cells align away from the direction of the applied stretch; for high frequencies cells align nearly perpendicular to the strain direction 3. Using a simple analytical model that includes the forces due to both the mechano-sensitive nature of cells and the elastic response of the matrix, we explain several long-standing and universal puzzles associated with the elasticity of cell-containing gels. Our model, that contains only two dimensionless parameters that can be measured by force experiments, predicts many features observed in measurements of cellular forces and orientation including the increase with time in the forces generated by cells in the absence of applied stress and the consequent decrease of the forces in the presence of quasi-static stresses. We also explain the puzzling observation of parallel alignment of cells for static and quasi-static applied stresses and the nearly perpendicular alignment of cells for dynamically varying stresses. More importantly, we predict how cell orientation varies as a function of the frequency of cyclically varying stresses and identify the various time scales that are involved; this, we believe will permit better control of the experimental systems related to tissue engineering in the future. References:\\ 1) Discher D. E., Janmey P., and Wang Y., Science, vol. 310, pp 1139 (2005); Engler A. J., Sen S., Sweeney H. L. and Discher D. Cell, Vol. 126, pp 677 (2006).\\ 2) Eastwood M., Mudera V. C., McGrouther D.A., and Brown R.A., Cell Motil. Cytoskeleton, vol 40, pp 13 (1998).\\ 3) Wang J. H-C.,Goldschmidt-Clermont P., and Wille J., J. Biomech., vol 34, pp 1563 (2001); Kurpunski K., Chu J., Hashi C., and Li S., PNAS, vol 103, pp 16095 (2006).

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