Topographic Cues Guiding Cell Polarization via Distinct Cellular Mechanosensing Pathways

Abstract

Cell polarization exists in a variety of tissues to regulate cell behaviors and functions. Space constraint (spatially limiting cell extension) and adhesion induction (guiding adhesome growth) are two main ways to induce cell polarization according to the microenvironment topographies. However, the mechanism of cell polarization induced by these two ways and the downstream effects on cell functions are yet to be understood. Here, space constraint and adhesion induction guiding cell polarization are achieved by substrate groove arrays in micro and nano size, respectively. Although the morphology of polarized cells is similar on both structures, the signaling pathways to induce the cell polarization and the downstream functions are distinctly different. The adhesion induction (nano‐groove) leads to the formation of focal adhesions and activates the RhoA/ROCK pathway to enhance the myosin‐based intracellular force, while the space constraint (micro‐groove) only activates the formation of pseudopodia. The enhanced intracellular force caused by adhesion induction inhibits the chromatin condensation, which promotes the osteogenic differentiation of stem cells. This study presents an overview of cell polarization and mechanosensing at biointerface to aid in the design of novel biomaterials.

Electrospun nanofibers for bone regeneration: from biomimetic composition, structure to function

“…4A). 162 In tissue engineering fields, electrospun nanofibers with aligned structures can be fabricated to play the role of a natural ECM to provide sites for cell adhesion, modulate cell behavior and improve mechanical strength (Fig. 4B).…”

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

“…Previously, research has shown that cell spreading and polarization may be caused by two different mechanisms, including space constraint and adhesion induction. 61 Nanogrooved substrates induce cellular polarization via focal adhesion formation and enhancement of intracellular traction forces via RhoA/ROCK activation. 61 On the other hand, cells on microgrooved substrates, which trigger cellular polarization via spatial constraint, acquire almost no visible focal adhesions but only directionless pseudopodia-based adhesion.…”

“…61 Nanogrooved substrates induce cellular polarization via focal adhesion formation and enhancement of intracellular traction forces via RhoA/ROCK activation. 61 On the other hand, cells on microgrooved substrates, which trigger cellular polarization via spatial constraint, acquire almost no visible focal adhesions but only directionless pseudopodia-based adhesion. The increased cell stiffness observed on our microgrooved platforms via AFM is proposed to be a reflection of cell tension unrelated to focal adhesion-exerted intracellular traction forces.…”

Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung

“…Several studies have investigated the mechanisms that regulate cellular structure, function, proliferation, differentiation, secretion, movement, and metabolism in response to mechanical stimulation by physical forces (Liao et al, 2020;Liu et al, 2021). Aberrant mechanical stretching can result in cellular barrier dysfunction, metabolic dysfunction, cytotoxicity, and inflammation (Figure 1).…”