Abstract
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.
Highlights
The extracellular matrix (ECM) is most commonly defined as the non-cellular component of tissue that provides both biochemical and essential structural support for its cellular constituents
Collins et al [122] recently demonstrated that the ability of platelet endothelial cell adhesion molecule-1 (PECAM-1) to respond to mechanical forces is influenced by the type of ECM they are adhered to
In mammalian systems, matrix elasticity and cell-spreading geometry are noted to heavily regulate yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) nuclear transport and their corresponding physiological processes [157]. These results suggest that focal adhesion and cytoskeleton-mediated cell signalling of mechanical rigidity is coupled to the YAP/TAZ pathway to induce metastasis and tumour invasion, indicating a direct chemical pathway linking mechanical force with malignant cellular behaviour
Summary
The extracellular matrix (ECM) is most commonly defined as the non-cellular component of tissue that provides both biochemical and essential structural support for its cellular constituents. Every organ has a unique composition of these elements to serve a particular tissue-specific purpose [1,2] This unique composition arises through dynamic biophysical and biochemical feedback between cellular components and their evolving microenvironment during tissue development [3,4]. Cells have been shown to transduce cues from the ECM, such as spatial context and mechanical rigidity, to coordinate crucial morphological organization and signalling events through regulation of gene transcription. This process in which a cell converts external mechanical stimuli into a downstream intracellular chemical signal is known as mechanotransduction [10]. Different subtypes and combinations of ECM molecules confer different functions that are essential for the whole body to function
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