Cytoskeleton and plasma-membrane damage resulting from exposure to sustained deformations: A review of the mechanobiology of chronic wounds

The purpose of this review paper is to summarize the current knowledge on cell-scale mechanically-inflicted deformation-damage, which is at the frontier of cell mechanobiology and biomechanics science, specifically in the context of chronic wounds. The dynamics of the mechanostructure of cells and particularly, the damage occurring to the cytoskeleton and plasma-membrane when cells are chronically deformed (as in a weight-bearing static posture) is correlated to formation of the most common chronic wounds and injuries, such as pressure ulcers (injuries). The first occurrence is microscopic injury which onsets as damage in individual cells and then progresses macroscopically to the tissue-scale. Here, we specifically focus on sub-catastrophic and catastrophic damage to cells that can result from mechanical loads that are delivered statically or at physiological rates; this results in apoptosis at prolonged times or necrosis, rapidly. We start by providing a basic background of cell mechanics and dynamics, focusing on the plasma-membrane and the cytoskeleton, and discuss approaches to apply and estimate deformations in cells. We then consider the effects of different levels of mechanical loads, i.e. low, high and intermediate, and describe the expected damage in terms of time-scales of application and in terms of cell response, providing experimental examples where available. Finally, we review different theoretical and computational modeling approaches that have been used to describe cell responses to sustained deformation. We highlight the insights that those models provide to explain, for example, experimentally observed variabilities in cell damage and death under loading.