Shear stress generated by blood flow is continuously exerted on vascular endothelial cells. The force is essential for the proper development of the cardiovascular system and for maintaining stable, healthy blood vessels. The cover image of the May 5 issue of Biophysical Journal demonstrates that shear stress induces concentration gradients of membrane proteins in living cells.
In the cover image, shear stress was applied to cells cultured in flow chambers by exposing them to a left-to-right flow of culture medium. The images show the distribution of EGFP-tagged membrane proteins in living cells, acquired by using an epifluorescence microscope. By overlaying images taken before (blue or green) and after (magenta or red) the onset of flow, we compare how the distribution of membrane proteins changes in response to shear stress. As shown, membrane proteins become concentrated on the downstream (right) side after flow application. Notably, shear stress at levels comparable to those experienced by endothelial cells in arteries is sufficient to induce this gradient formation of membrane proteins.
In this work, we demonstrate that shear stress induces concentration gradients of both glycosylphosphatidylinositol (GPI)-anchored proteins and transmembrane proteins, including receptors and adhesion proteins. Furthermore, single-molecule live-cell imaging under shear stress reveals that GPI-anchored proteins exhibit diffusion with a drift in the direction of flow. These findings suggest that external flow directly drives the movement of diverse membrane proteins, leading to the formation of concentration gradients.
Various cell types, including endothelial cells, fibroblasts, and neutrophils, can sense external fluid flow and respond by changing their shape and migrating in the direction of flow. However, the mechanism by which cells detect the direction of flow remains incompletely understood. Shear stress–induced concentration gradients of membrane proteins may play an important role in this flow-sensing process.
Learn more about our work at https://www.lif.kyoto-u.ac.jp/e/research/lab/5097/and https://sites.google.com/a/lehigh.edu/honerkamp-smith/honerkamp-smith-homepage.
— Sawako Yamashiro, Misato Nomura, Nils Chapin, Sreeja Sasidharan, Louis Elverston, Kohjiro Nagao, Leah Knepper, Damien Thévenin, Naoki Watanabe, and Aurelia R. Honerkamp-Smith