Gravity plays a central role in vertebrate development and evolution. Gravitational forces acting on mammalian tissues cause the net muscle forces required for locomotion to be higher on earth than on a body subjected to a microgravitational field. As body mass increases during development, the musculoskeleton must be able to adapt by increasing the size of its functional units. Thus mechanical forces required to do the work (mechanical energy) of locomotion must be sensed by cells and converted into chemical energy (synthesis of new tissue). Extracellular matrices (ECMs) are multicomponent tissues that transduce internal and external mechanical signals into changes in tissue structure and function through a process termed mechanochemical transduction. Under the influence of an external gravitational field, both mineralized and unmineralized vertebrate tissues exhibit internal tensile forces that serve to preserve a synthetic phenotype in the resident cell population. Application of additional external forces alters the balance between the external gravitational force and internal forces acting on resident cells leading to changes in the expression of genes and production of protein that ultimately may alter the exact structure and function of the extracellular matrix. Changes in the equilibrium between internal and external forces acting on ECMs and changes in mechanochemical transduction processes at the cellular level appear to be important mechanisms by which mammals adjust their needs to store, transmit, and dissipate energy that is required during development and for bodily movements. Mechanosensing is postulated to involve many different cellular and extracellular components. Mechanical forces cause direct stretching of protein-cell surface integrin binding sites that occur on all eukaryotic cells. Stress-induced conformational changes in the extracellular matrix may alter integrin structure and lead to activation of several secondary messenger pathways within the cell. Activation of these pathways leads to altered regulation of genes that synthesize and catabolize extracellular matrix proteins as well as to alterations in cell division. Another aspect by which mechanal signals are transduced involves deformation of gap junctions containing calcium-sensitive stretch receptors. Once activated, these channels trigger secondary messenger activation through pathways similar to those involved in integrin-dependent activation and allow cell-to-cell communications between cells with similar and different phenotypes. Another process by which mechanochemical transduction occurs is through the activation of ion channels in the cell membrane. Mechanical forces have been shown to alter cell membrane ion channel permeability associated with Ca⁺² and other ion fluxes. In addition, the application of mechanical forces to cells leads to the activation of growth factor and hormone receptors even in the absence of ligand binding. These are some of the mechanisms that have evolved in vertebrates by which cells respond to changes in external forces that lead to changes in tissue structure and function.

Collagen and proteoglycans work in unison in the ECM to bear loads, store elastic energy and then dissipate excess energy to avoid tissue fatigue and premature mechanical failure. While collagen fibers store elastic energy by stretching the flexible regions in the triple helix, they do so by lowering their free energy through a reduction in the entropy and a decrease in charge–charge repulsion. Entropic increases occur when the load is released that drive the reversibility of the process and transmission of excess energy. Energy is dissipated by sliding of collagen fibrils by each other with the aid of decorin molecules that reside on the d and e bands of the native D repeat pattern. Fluid flow from the hydration layer associated with the decorin and collagen fibrils hydraulically dissipates energy during sliding. The deformation is reversed by osmotic forces that cause fluid to reform a hydration shell around the collagen fibrils when the loads are removed. In this paper a model is presented describing the organization of collagen fibers in the skin and cell–collagen mechanical relationships that exist based on non-invasive measurements made using vibrational optical coherence tomography. It is proposed that under external stress, collagen fibers form a tensional network in the plane of the skin. Collagen fiber tension along with forces generated by fibroblasts exerted on collagen fibers lead to an elastic modulus that is almost uniform throughout the plane of the skin. Tensile forces acting on cells and tissues may provide a baseline for stimulation of normal mechanotransduction. We hypothesize that during aging, changes in cellular metabolism, cell–collagen interactions and light and UV light exposure cause down regulation of mechanotransduction and tissue metabolism leading to tissue atrophy.