Petzold Jonna, Gentleman Eileen
Centre for Craniofacial and Regenerative Biology, King's College London, London, United Kingdom.
Front Cell Dev Biol. 2021 Nov 8;9:761871. doi: 10.3389/fcell.2021.761871. eCollection 2021.
Although understanding how soluble cues direct cellular processes revolutionised the study of cell biology in the second half of the 20th century, over the last two decades, new insights into how mechanical cues similarly impact cell fate decisions has gained momentum. During development, extrinsic cues such as fluid flow, shear stress and compressive forces are essential for normal embryogenesis to proceed. Indeed, both adult and embryonic stem cells can respond to applied forces, but they can also detect intrinsic mechanical cues from their surrounding environment, such as the stiffness of the extracellular matrix, which impacts differentiation and morphogenesis. Cells can detect changes in their mechanical environment using cell surface receptors such as integrins and focal adhesions. Moreover, dynamic rearrangements of the cytoskeleton have been identified as a key means by which forces are transmitted from the extracellular matrix to the cell and Although we have some understanding of the downstream mechanisms whereby mechanical cues are translated into changes in cell behaviour, many of the signalling pathways remain to be defined. This review discusses the importance of intrinsic mechanical cues on adult cell fate decisions, the emerging roles of cell surface mechano-sensors and the cytoskeleton in enabling cells to sense its microenvironment, and the role of intracellular signalling in translating mechanical cues into transcriptional outputs. In addition, the contribution of mechanical cues to fundamental processes during embryogenesis such as apical constriction and convergent extension is discussed. The continued development of tools to measure the biomechanical properties of soft tissues is likely to uncover currently underestimated contributions of these cues to adult stem cell fate decisions and embryogenesis, and may inform on regenerative strategies for tissue repair.
尽管了解可溶性信号如何指导细胞过程在20世纪下半叶彻底改变了细胞生物学的研究，但在过去二十年中，关于机械信号如何同样影响细胞命运决定的新见解也日益受到关注。在发育过程中，诸如流体流动、剪切应力和压缩力等外在信号对于正常胚胎发生的进行至关重要。事实上，成体干细胞和胚胎干细胞都能对施加的力作出反应，但它们也能检测来自周围环境的内在机械信号，比如细胞外基质的硬度，这会影响细胞分化和形态发生。细胞可以利用整合素和粘着斑等细胞表面受体来检测其机械环境的变化。此外，细胞骨架的动态重排已被确定为将力从细胞外基质传递到细胞的关键方式，并且尽管我们对机械信号转化为细胞行为变化的下游机制有了一些了解，但许多信号通路仍有待明确。本综述讨论了内在机械信号对成体细胞命运决定的重要性、细胞表面机械传感器和细胞骨架在使细胞感知其微环境方面的新作用，以及细胞内信号在将机械信号转化为转录输出方面的作用。此外，还讨论了机械信号在胚胎发生过程中的基本过程，如顶端收缩和汇聚延伸中的作用。测量软组织生物力学特性的工具的持续发展可能会揭示这些信号目前被低估的对成体干细胞命运决定和胚胎发生的贡献，并可能为组织修复的再生策略提供信息。
