Open Access

REVIEW

Do tensile and shear forces exerted on cells influence mechanotransduction through stored energy considerations?

by FREDERICK H. SILVER^1,2,*, TANMAY DESHMUKH²

1 Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
2 OptoVibronex, LLC., Ben Franklin Tech Partners, Bethlehem, PA 18015, USA

* Corresponding Author: FREDERICK H. SILVER. Email:

BIOCELL 2024, 48(4), 525-540. https://doi.org/10.32604/biocell.2024.047965

Received 23 November 2023; Accepted 26 February 2024; Issue published 09 April 2024

Abstract

All tissues in the body are subjected externally to gravity and internally by collagen fibril and cellular retractive forces that create stress and energy equilibrium required for homeostasis. Mechanotransduction involves mechanical work (force through a distance) and energy storage as kinetic and potential energy. This leads to changes in cell mitosis or apoptosis and the synthesis or loss of tissue components. It involves the application of energy directly to cells through integrin-mediated processes, cell-cell connections, stretching of the cell cytoplasm, and activation of the cell nucleus via yes-associated protein (YAP) and transcriptional coactivator with PDZ-motif (TAZ). These processes involve numerous complexes, intermediate molecules, and multiple pathways. Several pathways have been identified from research studies on vertebrate cell culture and from studies in invertebrates. These pathways involve mechanosensors and other molecules that activate the pathways. This review discusses the mitogen-activated protein kinase (MAPK) family, Hippo, Hedgehog, and Wingless-related integration site (WNT)/β catenin signaling pathways. The mediators covered include β catenin, ion channels, growth factors, hormone receptors, members of the Ras superfamily, and components of the linker of nucleoskeleton and cytoskeleton (LINC) complex. However, the interrelationship among the different pathways remains to be clarified. Integrin-mediated mechanotransduction involves direct tensile loading and energy applied to the cell membrane via collagen fibril stretching. This energy is transferred between cells by stretching the cell-cell connections involving cadherins and the WNT/β catenin pathway. These alterations induce changes in intracellular events in the cytoskeleton and nuclear skeleton caused by the release of YAP and TAZ. These coactivators then penetrate through the nuclear pores and influence nuclear cell function. Alteration in the balance of forces and energy applied to cells and tissues is hypothesized to shift the cell-extracellular matrix mechanical equilibrium by modifying mechanotransduction. The shift in equilibrium can lead to either tissue synthesis, genetic modifications, or promote fibrotic diseases, including epithelial cell-derived cancers, depending on the local metabolic conditions.

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