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Back to the Mechanics vs. Biochemistry in Cellular Mechanotransduction

Alexander A. Spector's picture

In his interesting response to our comment posted on 11/28, Ning Wang focused on the transmission of a local force generated at the adhesion site(s). We agree that this is a question important to our understanding of the signaling to the nucleus. The question is not only about the range of the force transmission but also about the magnitude of such force because the nucleus is several times stiffer than the cytoskeleton. In our recent study of the nuclear deformation caused by changes in the apparent adhesion area in endothelial cells (Jean et al., J. Biomech. Eng, 2005), we found that the cell passive deformation is not sufficient to deform the nucleus at the level observed in the experiment. We introduced active forces generated inside the cell along the stress fibers and presumably associated with the actin/myosin interaction. We reproduced the experimental level of the nuclear strains when the active forces were on the order of magnitude of traction forces. It seems that the nuclear deformation resulting from perturbations of the adhesion sites is a fact confirmed by several groups under different conditions (e.g., Thomas et al., PNAS, 2002; Yim et al., Biomaterials, 2005). Also, numerous images show the deformed nuclei surrounded by the cytoskeletal meshwork: thus, it seems natural to assume that the nucleus is deformed by the cytoskeleton. If it is, the major remaining question is what cytoskeletal components are involved in this phenomenon and how they apply force to the nucleus. Of course, these forces are generated and transmitted via interconnected mechanical and biochemical pathways. Some of the scenarios are: some stress fibers end at the nuclear surface; or stress fibers begin and end at focal adhesion sites, but they go around the nucleus and deform it if an active force is generated along the fibers; or the microtubulus (Lee et al., Molec. Biol. Cell, 2005) are involved too. In any case, this is an interesting application of solid mechanics from both the constitutive and computational standpoint.

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Ning Wang's picture

The findings of Spector and colleagues that active forces (the prestress) in the cell are important for nuclear deformation are consistent with our experimental results in living cells (Hu et al, 2005) and modelings (Wang and Suo, 2005).  We have also proposed and provided experimental evidence that the prestress in the cytoskeleton dictates the shear stiffness of the cell (Wang et al, 2001, 2002) and gene expression (J Chen et al, AJP Cell, 2001).  Earlier work from our lab is also consistent with this hypothesis (Hubmayr et al, 1996, Pourati et al, 1998).  I agree that more work is needed in sorting out the structural basis for nuclear and intranuclear deformation.

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