Department of Biomedical Engineering, Boston University, Boston, USA.
Compr Physiol. 2011 Jan;1(1):499-524. doi: 10.1002/cphy.c100019.
An outstanding problem in cell biology is how cells sense mechanical forces and how those forces affect cellular functions. During past decades, it has become evident that the deformable cytoskeleton (CSK), an intracellular network of various filamentous biopolymers, provides a physical basis for transducing mechanical signals into biochemical responses. To understand how mechanical forces regulate cellular functions, it is necessary to first understand how the CSK develops mechanical stresses in response to applied forces, and how those stresses are propagated through the CSK where various signaling molecules are immobilized. New experimental techniques have been developed to quantify cytoskeletal mechanics, which together with new computational approaches have given rise to new theories and models for describing mechanics of living cells. In this article, we discuss current understanding of cell biomechanics by focusing on the biophysical mechanisms that are responsible for the development and transmission of mechanical stresses in the cell and their effect on cellular functions. We compare and contrast various theories and models of cytoskeletal mechanics, emphasizing common mechanisms that those theories are built upon, while not ignoring irreconcilable differences. We highlight most recent advances in the understanding of mechanotransduction in the cytoplasm of living cells and the central role of the cytoskeletal prestress in propagating mechanical forces along the cytoskeletal filaments to activate cytoplasmic enzymes. It is anticipated that advances in cell mechanics will help developing novel therapeutics to treat pulmonary diseases like asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease.
细胞生物学中的一个突出问题是细胞如何感知机械力以及这些力如何影响细胞功能。在过去的几十年中,已经明显的是,可变形的细胞骨架(CSK),即各种丝状生物聚合物的细胞内网络,为将机械信号转导为生化反应提供了物理基础。为了理解机械力如何调节细胞功能,首先有必要了解 CSK 如何响应施加的力产生机械应力,以及这些力如何在 CSK 中传播,在 CSK 中各种信号分子被固定。已经开发出了新的实验技术来量化细胞骨架力学,这些技术与新的计算方法一起,为描述活细胞的力学提供了新的理论和模型。在本文中,我们通过关注负责细胞中机械应力的发展和传递的生物物理机制及其对细胞功能的影响,来讨论细胞生物力学的当前理解。我们比较和对比了细胞骨架力学的各种理论和模型,强调了这些理论所依据的共同机制,同时也没有忽略不可调和的差异。我们突出了最近在理解活细胞细胞质中的力学转导方面的进展,以及细胞骨架预应力在沿着细胞骨架丝传播机械力以激活细胞质酶方面的核心作用。预计细胞力学的进展将有助于开发治疗哮喘、肺纤维化和慢性阻塞性肺疾病等肺部疾病的新疗法。