Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
Int J Mol Sci. 2018 Oct 4;19(10):3028. doi: 10.3390/ijms19103028.
The immense diversity of extracellular matrix (ECM) proteins confers distinct biochemical and biophysical properties that influence cell phenotype. The ECM is highly dynamic as it is constantly deposited, remodelled, and degraded during development until maturity to maintain tissue homeostasis. The ECM's composition and organization are spatiotemporally regulated to control cell behaviour and differentiation, but dysregulation of ECM dynamics leads to the development of diseases such as cancer. The chemical cues presented by the ECM have been appreciated as key drivers for both development and cancer progression. However, the mechanical forces present due to the ECM have been largely ignored but recently recognized to play critical roles in disease progression and malignant cell behaviour. Here, we review the ways in which biophysical forces of the microenvironment influence biochemical regulation and cell phenotype during key stages of human development and cancer progression.
细胞外基质 (ECM) 蛋白的巨大多样性赋予了其独特的生化和物理特性,从而影响细胞表型。ECM 非常动态,因为它在发育过程中不断被沉积、重塑和降解,直到成熟以维持组织内稳态。ECM 的组成和组织是时空调节的,以控制细胞行为和分化,但 ECM 动力学的失调会导致癌症等疾病的发展。ECM 提供的化学线索已被认为是发育和癌症进展的关键驱动因素。然而,由于 ECM 产生的机械力在很大程度上被忽视,但最近被认为在疾病进展和恶性细胞行为中发挥关键作用。在这里,我们回顾了微环境的生物物理力在人类发育和癌症进展的关键阶段如何影响生化调节和细胞表型。