Institute for Medicine and Engineering, University of Pennsylvania, 1010 Vagelos Laboratories, 3340 Smith Walk, PA 19104, USA.
J Cell Sci. 2011 Jan 1;124(Pt 1):9-18. doi: 10.1242/jcs.071001.
The responses of cells to chemical signals are relatively well characterized and understood. Cells also respond to mechanical signals in the form of externally applied force and forces generated by cell-matrix and cell-cell contacts. Many features of cell function that are generally considered to be under the control of chemical stimuli, such as motility, proliferation, differentiation and survival, can also be altered by changes in the stiffness of the substrate to which the cells are adhered, even when their chemical environment remains unchanged. Many examples from clinical and whole animal studies have shown that changes in tissue stiffness are related to specific disease characteristics and that efforts to restore normal tissue mechanics have the potential to reverse or prevent cell dysfunction and disease. How cells detect stiffness is largely unknown, but the cellular structures that measure stiffness and the general principles by which they work are beginning to be revealed. This Commentary highlights selected recent reports of mechanical signaling during disease development, discusses open questions regarding the physical mechanisms by which cells sense stiffness, and examines the relationship between studies in vitro on flat substrates and the more complex three-dimensional setting in vivo.
细胞对化学信号的反应相对来说特征明确，也容易理解。细胞还会对外部施加的力以及细胞-基质和细胞-细胞接触产生的力等机械信号做出反应。一般认为，许多受化学刺激控制的细胞功能特征，如运动性、增殖、分化和存活，也可以通过改变细胞附着的基质的刚度来改变，即使它们的化学环境保持不变。许多来自临床和全动物研究的例子表明，组织硬度的变化与特定的疾病特征有关，并且努力恢复正常的组织力学特性有可能逆转或预防细胞功能障碍和疾病。细胞如何检测硬度在很大程度上是未知的，但测量硬度的细胞结构以及它们工作的一般原理开始被揭示。本评论重点介绍了疾病发展过程中机械信号传递的一些最新报告，讨论了细胞感知硬度的物理机制方面的悬而未决的问题，并研究了体外在平面基底上进行的研究与体内更复杂的三维环境之间的关系。
