SIGNIFICANCE: Stiffness of endothelial cells is closely linked to the function of the vasculature as it regulates the release of vasoactive substances such as nitric oxide (NO) and reactive oxygen species. The outer layer of endothelial cells, consisting of the glycocalyx above and the cortical zone beneath the plasma membrane, is a vulnerable compartment able to adapt its nanomechanical properties to any changes of forces exerted by the adjacent blood stream. Sustained stiffening of this layer contributes to the development of endothelial dysfunction and vascular pathologies. Recent Advances: The development of specific techniques to quantify the mechanical properties of cells enables the detailed investigation of the mechanistic link between structure and function of cells.
CRITICAL ISSUES: Challenging the mechanical stiffness of cells, for instance, by inflammatory mediators can lead to the development of endothelial dysfunction. Prevention of sustained stiffening of the outer layer of endothelial cells in turn improves endothelial function.
FUTURE DIRECTIONS: The mechanical properties of cells can be used as critical marker and test system for the proper function of the vascular system. Pharmacological substances, which are able to improve endothelial nanomechanics and function, could take a new importance in the prevention and treatment of vascular diseases. Thus, detailed knowledge acquisition about the structure/function relationship of endothelial cells and the underlying signaling pathways should be promoted. Antioxid. Redox Signal. 00, 000-000.