Mapping the dynamics of shear stress-induced structural changes in endothelial cells

Area of Science:

• Cell Biology
• Biophysics
• Mechanobiology

Background:

• Endothelial cells sense and respond to hemodynamic shear stress.
• Shear stress influences cytoskeletal dynamics, focal adhesion turnover, and extracellular matrix (ECM) assembly.
• Previous studies suggest shear stress impacts cellular structure, but rapid, coordinated changes are not fully understood.

Purpose of the Study:

• To investigate the rapid, coordinated structural dynamics of the cytoskeleton, focal adhesions, and ECM in response to shear stress onset.
• To determine the time scale of these cellular responses.
• To elucidate the role of cell density in shear stress-induced structural remodeling.

Main Methods:

• Utilized multiwavelength four-dimensional fluorescence microscopy.
• Tracked fluorescently labeled actin, vimentin, paxillin, vinculin, and fibronectin in aortic endothelial cells.
• Measured structural displacements before and after the onset of steady unidirectional shear stress.

Main Results:

• Shear stress increased actin polymerization into lamellipodia and altered stress fiber and vimentin filament displacement.
• New focal complexes formed, and remodeling of focal adhesions decreased in areas of actin polymerization.
• Cell density influenced focal adhesion and fibronectin matrix dynamics; confluent cells showed rapid downstream displacement.

Conclusions:

• Shear stress induces rapid, spatially coordinated changes in endothelial cell cytoskeleton, focal adhesions, and ECM.
• These rapid structural dynamics are consistent with mechanical stress focusing at mechanotransduction sites.
• Cellular responses to shear stress are rapid, occurring on a time scale of minutes and varying with cell density.