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

All tissues in the body are subjected externally to gravity and internally by collagenfibril 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)/βcatenin signaling pathways.The mediators covered includeβcatenin,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 collagenfibril stretching.This energy is transferred between cells by stretching the cell-cell connections involving cadherins and the WNT/βcatenin 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 promotefibrotic diseases,including epithelial cell-derived cancers,depending on the local metabolic conditions.

Mechanotransduction-The relationship between gravity,cells and tensile loading in extracellular matrix

Gravity plays a central role in vertebrate development and evolution.Mechanotransduction involves the tensile tethering of veins and arteries,connections between the epidermis and dermis in skin,tensile stress concentrations that occur at tissue interfaces,cell-cell interactions,cell-collagen fiber stress transfer in extracellular matrix and fluid shear flow.While attention in the past has been directed at understanding the myriad of biochemical players associated with mechanotransduction pathways,less attention has been focused on determining the tensile mechanical behavior of tissues in vivo.Fibroblasts sit on the surface of collagen fibers in living skin and exert a retractile force on the fibers.This retractile force pulls against the tension in collagen fibers in skin.After fibroblast-collagen fiber interactions are altered either by changes in fibroblast adhesion or after formation of cancer associated fibroblasts,and changes in cell junctions,alterations in the retractive force leads to changes in mechanotransduction.The purpose of this paper is to present a model of tensile forces that occur at the fibroblast-collagen fiber interface and how these forces are important in extracellular matrix physiology in health and disease.