Molecular and Integrative Physiological Sciences, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
J Cell Sci. 2012 Dec 15;125(Pt 24):5974-83. doi: 10.1242/jcs.108886. Epub 2012 Oct 24.
The stiffness of the extracellular matrix exerts powerful effects on cell proliferation and differentiation, but the mechanisms transducing matrix stiffness into cellular fate decisions remain poorly understood. Two widely reported responses to matrix stiffening are increases in actomyosin contractility and cell proliferation. To delineate their relationship, we modulated cytoskeletal tension in cells grown across a physiological range of matrix stiffnesses. On both synthetic and naturally derived soft matrices, and across a panel of cell types, we observed a striking reversal of the effect of inhibiting actomyosin contractility, switching from the attenuation of proliferation on rigid substrates to the robust promotion of proliferation on soft matrices. Inhibiting contractility on soft matrices decoupled proliferation from cytoskeletal tension and focal adhesion organization, but not from cell spread area. Our results demonstrate that matrix stiffness and actomyosin contractility converge on cell spreading in an unexpected fashion to control a key aspect of cell fate.
细胞外基质的硬度对细胞增殖和分化有很大的影响，但将基质硬度转化为细胞命运决定的机制仍知之甚少。两种广泛报道的对基质变硬的反应是肌动球蛋白收缩力的增加和细胞增殖。为了阐明它们之间的关系，我们在细胞生长的生理范围内调节细胞骨架张力基质硬度。在合成的和天然衍生的软基质上，以及在一系列细胞类型中，我们观察到抑制肌动球蛋白收缩力的效果发生了惊人的逆转，从在刚性基质上增殖的减弱转变为在软基质上增殖的强烈促进。在软基质上抑制收缩力使增殖与细胞骨架张力和焦点黏附组织解耦，但与细胞铺展面积无关。我们的结果表明，基质硬度和肌动球蛋白收缩力以一种出人意料的方式集中在细胞铺展上，从而控制细胞命运的一个关键方面。
