Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
Sci Rep. 2013;3:1087. doi: 10.1038/srep01087. Epub 2013 Jan 18.
Cells continuously sense and respond to external mechanical forces through their cytoskeleton. Here we show that only a small subset of actin fibers, those forming the perinuclear actin cap that wraps around the nucleus, form in response to low physiological mechanical stresses in adherent fibroblasts. While conventional basal stress fibers form only past a threshold shear stress of 0.5 dyn/cm(2), actin-cap fibers are formed at shear stresses 50 times lower and orders-of-magnitude faster than biochemical stimulation. This fast differential response is uniquely mediated by focal adhesion protein zyxin at low shear stress and actomyosin fibers of the actin cap. We identify additional roles for lamin A/C of the nuclear lamina and linkers of nucleus to cytoskeleton (LINC) molecules nesprin2giant and nesprin3, which anchor actin cap fibers to the nucleus. These results suggest an interconnected physical pathway for mechanotransduction, from the extracellular milieu to the nucleus.
细胞通过细胞骨架不断感知和响应外部机械力。在这里，我们表明，只有一小部分肌动蛋白纤维，即形成围绕细胞核的核周肌动蛋白帽的那些纤维，会对贴壁成纤维细胞中低生理机械应激做出响应。虽然传统的基底应激纤维仅在剪切应力超过 0.5 dyn/cm²时才形成，但在剪切应力低 50 倍的情况下，肌动蛋白帽纤维形成的速度比生化刺激快几个数量级。这种快速的差异反应是由低剪切应力下的粘着斑蛋白 zyxin 和肌动球蛋白纤维的肌动蛋白帽唯一介导的。我们还确定了核纤层蛋白 A/C 和核骨架到细胞质连接蛋白（LINC）分子 nesprin2giant 和 nesprin3 的其他作用，它们将肌动蛋白帽纤维锚定在细胞核上。这些结果表明，从细胞外环境到细胞核，存在着一种相互关联的机械转导物理途径。
