Endothelial cells form the innermost layer of blood vessels and are continuously exposed to haemodynamic forces generated by blood flow. This unique position enables the vascular endothelium to sense and respond to mechanical stimuli, thereby regulating essential vascular functions. A key adaptive mechanism is the dynamic modulation of endothelial surface mechanics. Changes in endothelial stiffness directly affect the bioavailability of vasodilators such as nitric oxide (NO), with softer endothelial cells releasing more NO than stiffer cells. Thus, endothelial stiffness serves as an important indicator of cellular function and vascular health.
Our work has demonstrated that chronic stiffening of the endothelial surface contributes to endothelial dysfunction and vascular inflammation, two hallmarks of many cardiovascular diseases. We focus on the mechanical properties of the endothelial surface and their interaction with mechanosensitive ion channels. In particular, we investigate two mechanically distinct compartments: the endothelial glycocalyx (eGC), which forms the outermost surface layer, and the underlying actin-rich endothelial cortex located approximately 50–150 nm beneath the plasma membrane. Using atomic force microscopy (AFM)-based nanoindentation, we quantify the mechanical properties of these structures and assess their alterations under inflammatory conditions.
Beyond serving as structural elements, the endothelial glycocalyx and cortex are integral components of cellular mechanotransduction. Their mechanical properties are tightly linked to cytoskeletal dynamics and influence the activity of mechanosensitive proteins and ion channels. Since mechanosensitive ion channels are expressed in both endothelial and vascular smooth muscle cells, coordinated signalling between these cell layers is essential for the precise regulation of vascular tone and function. During the last years, we have focused on the endothelial ENaC and Piezo 1. We could show that the activity of these mechanosensitive ion channels determines endothelial mechanics and thus vascular function.
Our work aims to elucidate how endothelial mechanics and mechanosensitive ion channels interact to regulate vascular homeostasis and how their dysfunction contributes to cardiovascular disease. Particular emphasis is placed on the emerging concept that the endothelial surface represents a highly specialized mechanosensitive compartment and a potential therapeutic target in vascular pathologies. Understanding these mechanisms may open new avenues in the rapidly evolving fields of channelopathies and mechanomedicine.