Mechanical Signaling From ECMs to Nuclear Envelopes in Cell Transitions and Fate Decisions: A Review and Perspective on Adhesion-Niche-Based Anti-EndMT and Anti-EMT

Cells respond to extracellular matrices (ECMs) and generate internal signals associated with genomic and epigenomic changes. Currently, many studies employ direct intracellular chemical, genomic, or epigenomic modulation, which may not always be the optimal avenue for directing cell transitions and fate decisions in therapeutic contexts. This paper aims to conceptualize adhesion-niche-based mechanobiological strategies that are free from direct intracellular modulation, but effective in controlling cell transitions and fate decisions, such as endothelial-to-mesenchymal transition (EndMT), epithelial-to-mesenchymal transition (EMT), as well as reprogramming and differentiation processes associated with them. To this end, we review the molecular and biophysical mechanisms of cellular interactions with two-dimensional ECMs. Across ECMs, focal adhesions, the cytoplasm, and the nuclear envelope, we discuss how mechanical signals propagate and generate biological events. By providing an integrated picture of the mechanobiological responses of contractile cells on two-dimensional ECMs, our review offers novel perspectives on anti-EndMT and anti-EMT, based on adhesion-niche-dependent modulation of biphasic mechanotransduction.