联合起来:细胞力学转导中细胞骨架和细胞基质黏附的整合。
United we stand: integrating the actin cytoskeleton and cell-matrix adhesions in cellular mechanotransduction.
机构信息
BioQuant and Institute for Theoretical Physics, University of Heidelberg, Heidelberg, Germany.
出版信息
J Cell Sci. 2012 Jul 1;125(Pt 13):3051-60. doi: 10.1242/jcs.093716. Epub 2012 Jul 13.
Many essential cellular functions in health and disease are closely linked to the ability of cells to respond to mechanical forces. In the context of cell adhesion to the extracellular matrix, the forces that are generated within the actin cytoskeleton and transmitted through integrin-based focal adhesions are essential for the cellular response to environmental clues, such as the spatial distribution of adhesive ligands or matrix stiffness. Whereas substantial progress has been made in identifying mechanosensitive molecules that can transduce mechanical force into biochemical signals, much less is known about the nature of cytoskeletal force generation and transmission that regulates the magnitude, duration and spatial distribution of forces imposed on these mechanosensitive complexes. By focusing on cell-matrix adhesion to flat elastic substrates, on which traction forces can be measured with high temporal and spatial resolution, we discuss our current understanding of the physical mechanisms that integrate a large range of molecular mechanotransduction events on cellular scales. Physical limits of stability emerge as one important element of the cellular response that complements the structural changes affected by regulatory systems in response to mechanical processes.
许多健康和疾病中的重要细胞功能都与细胞响应机械力的能力密切相关。在细胞黏附到细胞外基质的情况下,肌动蛋白细胞骨架中产生的力,并通过整合素基焦点黏附传递的力,对于细胞对环境线索(如黏附配体的空间分布或基质硬度)的响应是至关重要的。虽然已经在鉴定可以将机械力转化为生化信号的机械敏感分子方面取得了相当大的进展,但对于调节施加在这些机械敏感复合物上的力的大小、持续时间和空间分布的细胞骨架力产生和传递的本质,我们知之甚少。通过关注细胞与基质的黏附到平坦的弹性底物上,在该底物上可以以高时间和空间分辨率测量牵引力,我们讨论了我们目前对整合细胞尺度上大量分子机械转导事件的物理机制的理解。稳定性的物理限制作为细胞响应的一个重要因素出现,补充了响应机械过程的调节系统所影响的结构变化。