The shear stress of it all: the cell membrane and mechanochemical transduction

Abstract

As the inner lining of the vessel wall, vascular endothelial cells are poised to act as a signal transduction interface between haemodynamic forces and the underlying vascular smooth-muscle cells. Detailed analyses of fluid mechanics in atherosclerosis-susceptible regions of the vasculature reveal a strong correlation between endothelial cell dysfunction and areas of low mean shear stress and oscillatory flow with flow recirculation. Conversely, steady shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. The molecular basis of shear-induced mechanochemical signal transduction and the endothelium's ability to discriminate between flow profiles remains largely unclear. Given that fluid shear stress does not involve a traditional receptor/ligand interaction, identification of the molecule(s) responsible for sensing fluid flow and mechanical force discrimination has been difficult. This review will provide an overview of the haemodynamic forces experienced by the vascular endothelium and its role in localizing atherosclerotic lesions within specific regions of the vasculature. Also reviewed are several recent lines of evidence suggesting that both changes in membrane microviscosity linked to heterotrimeric G proteins, and the transmission of tension across the cell membrane to the cell-cell junction where known shear-sensitive proteins are localized, may serve as the primary force-sensing elements of the cell.

Mechanical modulation of osteochondroprogenitor cell fate

“…Developmental context was defined by the manner in which density was achieved, which itself exerts a profound influence on the formation of multi-dimensional and multi-cellular structures (see above) [McBride 2007]. Similar observations have been noted in in vitro studies of endothelial cells, whose activity is modulated more significantly by temporal gradients in shear stress compared to the spatial gradient in shear stress magnitudes [White and Frangos 2007]. One might expect that a mesenchymal stem cell within a condensation is exposed to stress magnitudes that vary with the cell's position.…”

Concise Review: From Greenhouse to Garden: The Changing Soil of the Hematopoietic Stem Cell Microenvironment During Development

“…Nitric oxide production from endothelial cells is triggered by the sheer stress induced by pulsatile flow that occurs as a consequence of the heart beating [109]. Progenitor numbers from para-aortic splanchnopleura-derived cells (the precursor tissue of the AGM) from Ncx1 2/2 embryos, which lack a heartbeat, can be increased by exposure to shear stress that is equivalent to the hemodynamic shear stress experienced by the embryonic aorta at E10.5 [64].…”

Magnetic resonance imaging-based computational modelling of blood flow and nanomedicine deposition in patients with peripheral arterial disease

“…Figure insets represent magnification of the region downstream of the stenosis ('mean' slice) at various times during the cardiac cycle as departures from unidirectional flow are known to occur distal to stenosis [50]. The time evolution of the streamline trajectories in figure 4 clearly captures the pulsatile nature of the blood flow.…”

“…Furthermore, as vascular expression of CAMs is known to be sensitive to the temporal gradient of WSS [74], which can potentially influence CAM-targeted NP deposition patterns, it would be interesting to carry out a systematic analysis of this important quantity at critical geometric locations (e.g. recirculation zones distal to the stenosis) [50]. Additionally, extending the current analysis to the intermediate time points (six and 12 months) to investigate if any of the detected haemodynamic improvements occurred earlier in the post-operative process could provide important insights into PAD management.…”