Kaazempur Mofrad M R, Abdul-Rahim N A, Karcher H, Mack P J, Yap B, Kamm R D
Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Mass. Ave, NE47-321, Cambridge, MA 02139, USA.
Acta Biomater. 2005 May;1(3):281-93. doi: 10.1016/j.actbio.2005.02.008. Epub 2005 Mar 31.
Living cells respond to mechanical stimulation in a variety of ways that affect nearly every aspect of their function. Such responses can range from changes in cell morphology to activation of signaling cascades and changes in cell phenotype. Although the biochemical signaling pathways activated by mechanical stimulus have been extensively studied, little is known of the basic mechanisms by which mechanical force is transduced into a biochemical signal, or how the cell changes its behavior or properties in response to external or internal stresses. One hypothesis is that forces transmitted via individual proteins either at the site of cell adhesion to its surroundings or within the stress-bearing members of the cytoskeleton cause conformational changes that alter their binding affinity to other intracellular molecules. This altered equilibrium state can subsequently either initiate a biochemical signaling cascade or produce more immediate and local structural changes. To understand the phenomena related to mechanotransduction, the mechanics and chemistry of single molecules that form the signal transduction pathways must be examined. This paper presents a range of case studies that seek to explore the molecular basis of mechanical signal sensation and transduction, with particular attention to their macroscopic manifestation in the cell properties, e.g. in focal adhesion remodeling due to local application of force or changes in cytoskeletal rheology and remodeling due to cellular deformation.
活细胞以多种方式对机械刺激做出反应，这些反应几乎会影响其功能的方方面面。此类反应范围广泛，从细胞形态的改变到信号级联反应的激活以及细胞表型的变化。尽管机械刺激激活的生化信号通路已得到广泛研究，但对于机械力如何转化为生化信号，或者细胞如何响应外部或内部应力而改变其行为或特性的基本机制却知之甚少。一种假说认为，通过细胞与其周围环境黏附部位的单个蛋白质，或细胞骨架的应力承载成分传递的力会导致构象变化，从而改变它们与其他细胞内分子的结合亲和力。这种改变的平衡状态随后要么启动生化信号级联反应，要么产生更直接和局部的结构变化。为了理解与机械转导相关的现象，必须研究构成信号转导途径的单个分子的力学和化学性质。本文介绍了一系列案例研究，旨在探索机械信号感知和转导的分子基础，尤其关注它们在细胞特性中的宏观表现，例如由于局部施加力导致的粘着斑重塑，或由于细胞变形导致的细胞骨架流变学和重塑变化。
