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The structural integrity of cells under sustained mechanical deformations: The key for understanding pressure ulcers

Presented by: 
Amit Gefen
Monday 7th December 2015 - 14:15 to 15:00
INI Seminar Room 1
Sustained internal mechanical loads in tissues which develop during immobile weight-bearing postures such as while in bed or in a chair were identified as a fundamental cause for the onset and progression of pressure ulcers (PUs), particularly of the deep tissue injury (DTI) type. The sustained loading may compromise tissue viability either directly, by distorting cell shapes, or indirectly, by distorting the vasculature or lymphatic networks or, at the micro-scale, by distorting cellular organelles involved in regulating transport, e.g. the plasma membrane (PM). This talk will review our record of published research concerning the effects of sustained deformations across the different hierarchical scales: tissue-scale [cm], meso-scale [mm] and cell-scale [μm], with a focus on how sustained bodyweight loads eventually compromise homeostasis and cell viability. The evolution of our work to test our central hypothesis will be shown, specifically, that macroscopic tissue defo rmations translate to cell-level deformations and in particular, to localized tensile strains in the plasma membrane (PM) of cells. These localized PM stretches increase the permeability of the PM which, over time, could disrupt vital transport processes such as the function of ion channels, endocytosis and exocytosis. Viability of tissues exposed to sustained loading in the context of pressure ulcer development should therefore be investigated in all dimensional scales, from the macro to micro, and in particular at a cell scale, in order to provide complete understanding of the aetiology of PUs and DTIs and for identifying individuals for whom and conditions at which the susceptibility to these injuries might be greater. Emerging relevant methods of cell permeability quantification and modeling such as multiscale and multiphysics modeling will be highlighted, as they contribute substantially to the aetiological research in this field.
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University of Cambridge Research Councils UK
    Clay Mathematics Institute London Mathematical Society NM Rothschild and Sons