Influence of substrate topography on vascular endothelial cells

Vascular endothelial cells (ECs) in blood vessels are subjected to various biophysical cues that arise not only from the apical blood flow but also from the properties of the underlying vascular basement membrane (BM). How ECs integrate and respond to these cues, alone or combined, remains incompletely understood. In vivo, ECs are anchored to a vascular basement membrane (BM) that exhibits a topographical organization at different scales. We have been investigating the influence of surface structuration on ECs in vitro by using microgroove substrates as an idealized mimic of anisotropic BM topography. We have shown that microgrooves induce extensive nuclear deformations and control EC shape, alignment, and collective migration.
More recently, we have integrated microgroove substrates into a flow chamber to understand how ECs integrate both basal topography and apical flow. Our results show synergistic effects on EC orientation when grooves and flow are oriented in the same direction. On the other hand, orienting the grooves perpendicular to flow reveals a level of competition between the two biophysical cues, with the effect of the grooves on ECs becoming progressively more dominant as groove depth is increased. The current results underscore the importance of extracellular environment topography in the vascular system and point to interesting processes of cellular integration of multiple biophysical signals. From a more applied perspective, this work highlights the potential of using substrate topography to control endothelial behavior, with potentially interesting implications for the design of implantable vascular devices.