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The resistance of the liquid drop-like nucleus to deformation is dependent on whether the nuclear lamina is smooth or wrinkled. When it is smooth and taut, the nuclear shape can be calculated from geometric constraints on volume and surface area. 

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. 

In many tissues, cell type varies over single-cell length-scales, creating detailed heterogeneities fundamental to physiological function. To gain understanding of the relationship between tissue function and detailed structure, and eventually to engineer structurally and physiologically accurate tissues, we need the ability to assemble 3D cellular structures having the level of detail found in living tissue. Here we introduce a method of 3D cell assembly having a level of precision finer than the single-cell scale. With this method we create detailed cellular patterns, demonstrating that cell type can be varied over the single-cell scale and showing function after their assembly. 

During closed mitosis in fission yeast, growing microtubules push onto the nuclear envelope to deform it, which results in fission into two daughter nuclei. The resistance of the envelope to bending, quantified by the flexural stiffness, helps determine the microtubule-dependent nuclear shape transformations. Computational models of envelope mechanics have assumed values of the flexural stiffness of the envelope based on simple scaling arguments. The validity of these estimates is in doubt, however, owing to the complex structure of the nuclear envelope. Here, we performed computational analysis of the bending of the nuclear envelope under applied force using a model that accounts for envelope geometry. Our calculations show that the effective bending modulus of the nuclear envelope is an order of magnitude larger than a single membrane and approximately five times greater than the nuclear lamina. This large bending modulus is in part due to the 45 nm separation between the two membranes, which supports larger bending moments in the structure. Further, the effective bending modulus is highly sensitive to the geometry of the nuclear envelope, ranging from twofold to an order magnitude larger than the corresponding single membrane. These results suggest that spatial variations in geometry and mechanical environment of the envelope may cause a spatial distribution of flexural stiffness in the same nucleus. Overall, our calculations support the possibility that the nuclear envelope may balance significant mechanical stresses in yeast and in cells from higher organisms.