Monday, 11 October 2004 - 3:55 PM

This presentation is part of : Cellular Mechanics

Study of Endothelial Cell Rounding: Experiment, Analytical Estimates, and Computational Simulation

Ronald P. Jean, Christopher S. Chen, and Alexander A. Spector. Johns Hopkins University, 720 Rutland Ave., Baltimore, MD 21205

Cell shape, as well as the amount and strength of adhesion to the extracellular matrix, are known to control cell fate, including cell division, proliferation, and apoptosis. One mechanism of such control is through the transmission of traction forces distributed along adhesion sites, modulation of these forces by the active cytoskeleton, and generation of stresses in the nucleus, that could alter gene expression and protein synthesis. We analyze such a mechanical pathway by studying the process of cell rounding where originally spread endothelial cells were treated in order to detach them from the surface and cause their rounding. We imaged the nucleus and found that it also rounds. We quantified the process of the rounding of the nucleus and estimated the nuclear deformation as a function of time. Then we used the measured deformation to restore the force and stress fields around the nucleus. First, we applied an analytical model where the nucleus was treated as a compressible neo-Hookean material. The obtained estimates of the forces were of the same order of magnitude that traction forces previously measured by several groups. We also developed a comprehensive finite element analysis of cell rounding by using a model where the major components of the cell, including the membrane, nucleus, and active cytoskeleton (actin fiber network), were explicitly present. The computed forces deforming the nucleus have confirmed our preliminary analytical estimates. Finally, we analyze the stresses inside and along the nucleus to investigate how they can affect gene expression and protein synthesis.

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