Endothelial cells react to extracellular matrix (ECM) stiffness by increasing their contractility and permeability, which allows leukocyte transendothelial migration (TEM). However, intimal stiffening does not occur uniformly across the vasculature, and it is still poorly understood how the endothelium responds to these variations. Cynthia Reinhart-King and colleagues (VanderBurgh et al., 2020) now investigate how discrete variations in ECM stiffness affect neighbouring cells in an endothelial monolayer. Making use of a micropillar array composed of regions of different stiffness, the authors observe that TEM events occur in an oscillatory pattern that is symmetrical around the interface. TEM frequency fits a sinusoid as a function of the distance from the interface, where the peaks represent areas of compromised barrier function and increased contractility that are characterised by an increase in focal adhesions. Cell area and orientation within the monolayer also display an oscillatory pattern, with the sinusoid peaks representing larger cells perpendicular to the interface. Inhibiting or increasing contractility with pharmacological compounds disrupts the symmetry, amplitude and wavelength of the sinusoidal pattern of TEM; surprisingly, cell area and positioning are not affected by these treatments. This study thus sheds light on the effects of contractility on stiffness-mediated remodelling of cell adhesion and the collective response of cells to ECM variations.
