Matrix Stiffness: A Regulator of Cellular Behavior and Tissue Formation

Abstract

The extracellular environment is an essential mediator of cell health and provides both chemical and mechanical stimuli to influence single and collective cell behaviors. While historically there has been significant emphasis placed on chemical regulators within the extracellular matrix, the role of the mechanical environment is less well known. Here, we review the role of matrix mechanics on cell function and tissue integrity. Cellular responses to mechanical signals include differentiation, migration, proliferation, and alterations in cell-cell and cell-matrix adhesion. Interestingly, the mechanical properties of tissues are altered in many disease states, leading to cellular dysfunction and further disease progression. Successful regenerative medicine strategies must consider the native mechanical environment so that they are able to elicit a favorable cellular response and integrate into the native tissue structure.

Regulation of Endothelial Cell Adherence and Elastic Modulus by Substrate Stiffness

“…Increasing substrate stiffness has been generally reported to enhance cytoskeletal organization and result in the formation of more stable focal adhesions in association with cell shape alterations (Mason et al 2012). In accordance to this, we observed rounded cell morphologies with diffuse actin fibers on the soft substrate while cells cultured on the hard substrate exhibited more spread resting shapes with organized actin fibers.…”

“…Actin cytoskeletal organization and alignment is important in determining cell shape (Mason et al 2012). Increasing substrate stiffness has been generally reported to enhance cytoskeletal organization and result in the formation of more stable focal adhesions in association with cell shape alterations (Mason et al 2012).…”

“…On the other hand, diseased tissues exhibit altered mechanical properties which can disrupt the normal cellular function, such as ECM synthesis and cause further progression of the disease (Mason et al 2012). Cells sense mechanical cues from their surrounding environment and use various mechano-transducers, such as integrins, stretchactivated ion channels, primary cilia, and cytoskeleton to convert such signals to chemical stimuli which regulate their function (Wang 2006).…”

“…Unlike chemical cues, the effects of mechanical stimuli produced by extracellular environment on different cellular functions have not yet been fully studied. In vitro studies have reported that cells alter their cytoskeletal organization, mechanical properties, cellsubstrate adherence properties and other features to maintain, and regulate their functionality in response to changing substrate stiffness (Mason et al 2012).…”

An introduction to the wound healing assay using live-cell microscopy

“…30 In addition, the stiffness of the underlying substrate can also modulate the dynamics of the migration into the gap. 31 The dish or chamber used to culture the cells should be carefully chosen to match the experimental approach. Multi-well cell culture dishes (6, 12, or 24 wells) are a popular choice because they are inexpensive and fabricated from plastic treated to encourage cell adhesion.…”