The Effects of Stiffness, Fluid Viscosity, and Geometry of Microenvironment in Homeostasis, Aging, and Diseases: A Brief Review

Abstract

Cells sense biophysical cues in the micro-environment and respond to the cues biochemically and biophysically. Proper responses from cells are critical to maintain the homeostasis in the body. Abnormal biophysical cues will cause pathological development in the cells; pathological or aging cells, on the other hand, can alter their micro-environment to become abnormal. In this minireview, we discuss four important biophysical cues of the micro-environment-stiffness, curvature, extracellular matrix (ECM) architecture and viscosity-in terms of their roles in health, aging, and diseases.

Keywords: ECM architecture; aging; cancer; curvature; homeostasis; stiffness; viscosity.

Fig. 1

Cells change their movement modes on substrates withdifferent stiffness. (a) On stiff substrates, strong actomyosin–substrate coupling stretches mechanosensitive focal adhesion proteins, leading to the turnover of focal adhesions, a force-dependent process. (b) On soft substrates, weaker actomyosin–substrate coupling causes focal adhesion to be tugged backward, making more space between the membrane and the actin networks, allowing actin polymerization at the leading edge to drive the plasma membrane to expand forward.

Fig. 2

Curvature sensing at a multicellular scale. (a) On the flat surface, cell–cell tension generated by inward actomyosin contraction is balanced between two neighboring cells. Epithelium is securely attached to the substrate provided there is adequate cell–ECM adhesion. (b) On the concaved surface, the tension between two neighboring cells results in forces pointing to the direction of the apical side, stretching the bond between integrin and ECM. The actomyosin contractility at the apical side increases to achieve balance by counteracting the stretching force. If the stretching force cannot be balanced, epithelium with decreased cell–ECM adhesion strength will detach from the substrate.

Fig. 3

ECM alignment enhances stroma-ward diffusion of CAF-promoting factors, induces CAFs, and provides a track for CAFs to migrate toward the tumor. Left: initially, isotropic ECM limits diffusion of CAF-promoting factors. Right: aligned ECM by cancer cells allows CAF-promoting factors to diffuse more efficiently along the aligned ECM fibrils to reach stroma and induce stromal-residing cells to exhibit CAF phenotypes. The CAFs subsequently move toward the tumor along the aligned ECM fiber to further promote tumor progression.

Fig. 4

Physiological relevance of fluid viscosity in the human body