Editorial: Understanding molecular interactions that underpin vascular mechanobiology.

Cells are exposed to a variety of mechanical forces in their daily lives, especially endothelial cells that are stretched from vessel distention and are exposed to hemodynamic shear stress from a blood flow. Exposure to excessive forces can induce a disease, but the molecular details on how these cells perceive forces, transduce them into biochemical signals and genetic events, i.e., mechanotransduction, and integrate them into physiological or pathological changes remain unclear. However, seminal studies in endothelial cells over the past several decades have begun to elucidate some of these signals. These studies have been highlighted in APL Bioengineering and elsewhere, describing a complex temporal pattern where forces are sensed immediately by ion channels and force-dependent conformational changes in surface proteins, followed by biochemical cascades, cytoskeletal contraction, and nuclear remodeling that can affect long-term changes in endothelial morphology and fate. Key examples from the endothelial literature that have established these pathways include showing that integrins and Flk-1 or VE-cadherin act as shear stress transducers, activating downstream proteins such as Cbl and Nckβ or Src, respectively. In this Editorial, we summarize a recent literature highlighting these accomplishments, noting the engineering tools and analysis methods used in these discoveries while also highlighting unanswered questions.