Department of Biomedical Engineering, University of Virginia, 415 Lane Rd. MR5 1225, Charlottesville, VA, 22903, USA.
Adv Healthc Mater. 2020 Apr;9(8):e1901445. doi: 10.1002/adhm.201901445. Epub 2020 Feb 9.
Biophysical cues stemming from the extracellular environment are rapidly transduced into discernible chemical messages (mechanotransduction) that direct cellular activities-placing the extracellular matrix (ECM) as a potent regulator of cell behavior. Dynamic reciprocity between the cell and its associated matrix is essential to the maintenance of tissue homeostasis and dysregulation of both ECM mechanical signaling, via pathological ECM turnover, and internal mechanotransduction pathways contribute to disease progression. This review covers the current understandings of the key modes of signaling used by both the cell and ECM to coregulate one another. By taking an outside-in approach, the inherent complexities and regulatory processes at each level of signaling (ECM, plasma membrane, focal adhesion, and cytoplasm) are captured to give a comprehensive picture of the internal and external mechanoregulatory environment. Specific emphasis is placed on the focal adhesion complex which acts as a central hub of mechanical signaling, regulating cell spreading, migration, proliferation, and differentiation. In addition, a wealth of available knowledge on mechanotransduction is curated to generate an integrated signaling network encompassing the central components of the focal adhesion, cytoplasm and nucleus that act in concert to promote durotaxis, proliferation, and differentiation in a stiffness-dependent manner.
源自细胞外环境的生物物理线索迅速转化为可识别的化学信号（力学转导），指导细胞活动——将细胞外基质（ECM）作为细胞行为的有力调节剂。细胞与其相关基质之间的动态相互作用对于维持组织内稳态以及细胞外基质机械信号的失调至关重要，细胞外基质机械信号的失调通过病理性细胞外基质周转以及内部力学转导途径促进疾病进展。这篇综述涵盖了目前对细胞和细胞外基质相互核心调节彼此时使用的关键信号模式的理解。通过采用由外向内的方法，捕捉到信号转导每个层面（细胞外基质、质膜、黏着斑和细胞质）的固有复杂性和调节过程，以全面了解内部和外部机械调节环境。特别强调黏着斑复合物作为力学信号的中心枢纽，调节细胞铺展、迁移、增殖和分化。此外，还对大量可用的力学转导知识进行了精心整理，以生成一个综合信号网络，其中包含黏着斑、细胞质和细胞核的核心成分，它们协同作用以促进在依赖于刚度的方式下的趋硬性、增殖和分化。
