A biophysical view of the interplay between mechanical forces and signaling pathways during transendothelial cell migration

The vascular endothelium is exposed to an array of physical forces, including shear stress via blood flow, contact with other cells such as neighboring endothelial cells and leukocytes, and contact with the basement membrane. Endothelial cell morphology, protein expression, stiffness and cytoskeletal arrangement are all influenced by these mechanochemical forces. There are many biophysical tools that are useful in studying how forces are transmitted in endothelial cells, and these tools are also beginning to be used to investigate biophysical aspects of leukocyte transmigration, which is a ubiquitous mechanosensitive process. In particular, the stiffness of the substrate has been shown to have a significant impact on cellular behavior, and this is true for both endothelial cells and leukocytes. Thus, the stiffness of the basement membrane as an endothelial substrate, as well as the stiffness of the endothelium as a leukocyte substrate, is relevant to the process of transmigration. In this review, we discuss recent work that has related the biophysical aspects of endothelial cell interactions and leukocyte transmigration to the biochemical pathways and molecular interactions that take place during this process. Further use of biophysical tools to investigate the biological process of leukocyte transmigration will have implications for tissue engineering, as well as atherosclerosis, stroke and immune system disease research.