Figure 1.

High Gaussian curvature disrupts the nuclear lamina.

A. A-type and B-type lamins form juxtaposed networks inside the nuclear membrane. Lamin filaments are expected to stably interact with a membrane of low Gaussian curvature but to dissociate from a membrane with high Gaussian curvature (see ‘Single-filament model,’ Materials & Methods). R = radius of Gaussian curvature; R₁,R₂ = principal curvature radii. Lamin-A and lamin-B networks are thought to have differing material properties – and hence to dilute, or be depleted, at differing rates from regions of high nuclear curvature. B. Low-light imaging: A549 human lung cancer cells with RFP-lamin-B1 from monoallelic gene editing were transfected with GFP-lamin-A and live-imaged periodically over hours. Cell shape fluctuations transiently induced regions of high nuclear curvature. Intensity profiles: measured along the cell’s major axis, originating at the arrow head. Representative of 10 cells/20 nuclear poles; scale = 10 µm. C. Lamin-A and -B intensities were measured at the poles and sides of nuclei in three representative cells that rounded and/or elongated during live-imaging. Plots show lamin-B to lamin-A intensity ratio as a function of nuclear curvature. Insets: same data, fit with a sigmoidal function per our simple filament (un)binding model. Representative of 4 cells/8 nuclear poles. D. Live images of A549 mitosis, with the lamin-B network disassembling first and reassembling last at the higher-curvature poles of the nucleus (arrow heads).