Tensional homeostasis in dermal fibroblasts: Mechanical responses to mechanical loading in three-dimensional substrates

Abstract

Many soft connective tissues are under endogenous tension, and their resident cells generate considerable contractile forces on the extracellular matrix. The present work was aimed to determine quantitatively how fibroblasts, grown within three-dimensional collagen lattices, respond mechanically to precisely defined tensional loads. Forces generated in response to changes in applied load were measured using a tensional culture force monitor. In a number of variant systems, resident cells consistently reacted to modify the endogenous matrix tension in the opposite direction to externally applied loads. That is, increased external loading was followed immediately by a reduction in cell-mediated contraction whilst decreased external loading elicited increased contraction. Responses were cell-mediated and not a result of material properties of the matrices. This is the first detailed characterisation of a tensional homeostatic response in cells. The maintained force, after 8 h in culture, was typically around 40-60 dynes/million cells). Maintenance of an active tensional homeostasis has widespread implications for cells in culture and for whole tissue function.

Parametric study of effects of collagen turnover on the natural history of abdominal aortic aneurysms

“…Although it is not yet clear how cells regulate the deposition stretch, it would seem that actinomyosin activity would be needed, as migration or generation of 'tractional forces' can contribute to matrix remodelling [41]. Note, therefore, that actin (ACTA2) and myosin (MYH11) mutations have been reported in patients with thoracic aortic aneurysms [42,43].…”

Vascular Adaptation and Mechanical Homeostasis at Tissue, Cellular, and Sub-cellular Levels

“…They suggested that ''an equilibrium existed in the mechanical relationship of the cells with their support.'' Brown et al [92] confirmed these results, although they reported the endogenous force to be 0.5 nN per cell and that different periods were needed for the cells to restore the preferred mechanical state when perturbed from it. Subtle differences between studies are expected, of course, depending on initial collagen and cell density, type of cell, composition of the culture media, percent change in mechanical loading, and so forth.…”

A finite element model predicts the mechanotransduction response of tendon cells to cyclic tensile loading

“…Cells are known to respond to physical signals by way of a mechanotransduction tensegrity system, which connects the cell nucleus to the extracellular matrix through a cytoskeleton (Banes et al 1995;Brown et al 1998;Ingber 1997). Deformation of the cytoskeleton, via membrane anchored attachment proteins (integrins), or stimulation of other transmembrane proteins (G-protein receptors, receptor kinases, mitogen-activated protein kinases) (Wang 2006) initiates a cascade of gene expressions activating catabolic and/or anabolic cell responses (Lambert et al 1992;Mochitate et al 1991).…”