Butler Peter J
Department of Biomedical Engineering The Pennsylvania State University University Park, Pennsylvania 16802, USA.
APL Bioeng. 2020 Mar 3;4(1):010907. doi: 10.1063/1.5133645. eCollection 2020 Mar.
This Perspective paper advances a hypothesis of mechanosensation by endothelial cells in which the cell is a dynamic crowded system, driven by continuous enzyme activity, that can be shifted from one non-equilibrium state to another by external force. The nature of the shift will depend on the direction, rate of change, and magnitude of the force. Whether force induces a pathophysiological or physiological change in cell biology will be determined by whether the dynamics of a cellular system can accommodate the dynamics and magnitude of the force application. The complex interplay of non-static cytoskeletal structures governs internal cellular rheology, dynamic spatial reorganization, and chemical kinetics of proteins such as integrins, and a flaccid membrane that is dynamically supported; each may constitute the necessary dynamic properties able to sense external fluid shear stress and reorganize in two and three dimensions. The resulting reorganization of enzyme systems in the cell membrane and cytoplasm may drive the cell to a new physiological state. This review focuses on endothelial cell mechanotransduction of shear stress, but may lead to new avenues of investigation of mechanobiology in general requiring new tools for interrogation of mechanobiological systems, tools that will enable the synthesis of large amounts of spatial and temporal data at the molecular, cellular, and system levels.
这篇观点论文提出了一种内皮细胞机械传感假说，即细胞是一个动态拥挤的系统，由持续的酶活性驱动，外力可使其从一种非平衡状态转变为另一种非平衡状态。转变的性质将取决于力的方向、变化速率和大小。力是否会在细胞生物学中引起病理生理或生理变化，将取决于细胞系统的动力学是否能够适应力施加的动力学和大小。非静态细胞骨架结构的复杂相互作用控制着细胞内流变学、动态空间重组以及诸如整合素等蛋白质的化学动力学，还有动态支撑的松弛膜；每一个都可能构成能够感知外部流体剪切应力并在二维和三维空间中重组的必要动态特性。细胞膜和细胞质中酶系统的最终重组可能会将细胞驱动到一个新的生理状态。本综述聚焦于内皮细胞对剪切应力的机械转导，但可能会为一般的力学生物学研究开辟新途径，这需要用于研究力学生物系统的新工具，这些工具能够在分子、细胞和系统水平上合成大量的时空数据。
