Search for: All records

Cell migration through narrow spaces is essential in wound healing and metastatic spread of cancer. Cells must deform the large nucleus to fit through constricting channels. To understand the role of the nuclear lamina in limiting cell migration through constrictions, we imaged it in cells migrating through periodic constricting channels in a microdevice. The lamina underwent cycles of wrinkling and smoothing as the nucleus changed from an irregular, rounded shape in the wide channel regions between constrictions to a smooth, hourglass shape as the nucleus passed through the center of a constriction. The laminar surface area of nuclei within constrictions was measured to be at or above the computationally predicted threshold area for the nuclear volume. The channels excluded control nuclei that had insufficient excess surface area, but not nuclei lacking lamin A/C. Thus, the excess surface area of the nuclear lamina enables cell migration through constricting channels. 

ABSTRACT Shear stress imparted by blood flow tends to smoothen endothelial monolayers, a response classically attributed to reduced nuclear height and nuclear reorientation along flow. However, the mechanical basis remains unclear. Here, we tested predictions of the nuclear drop model—which posits that nuclear shape changes occur at constant volume and surface area—in human umbilical vein endothelial cells (HUVECs) under physiological shear stress. HUVEC nuclear morphologies varied from smooth, flat nuclei to wrinkled, tall ones. Applying shear stress reduced the frequency of tall, wrinkled nuclei, explaining the population‐level decrease in nuclear height. Lamin A/C–depleted nuclei are highly irregular and failed to recover shapes postindentation on PDMS microposts, suggesting that lamin A/C confers nuclear surface tension. Nuclear volume and surface area remained constant under shear, consistent with the drop model, and a computational model based on these constraints successfully predicted observed nuclear shapes. Neither lamin A/C nor lamin B1 depletion prevented shear‐induced YAP nuclear localization; instead, shear detached poorly spread cells, increasing spreading, focal adhesion assembly, and cytoskeletal tension in the remaining cells, thereby promoting YAP nuclear localization. These findings revise classical interpretations of flow‐induced endothelial smoothing and show that flow‐induced YAP nuclear localization results from increased cell spreading rather than nuclear deformation.