Fat-filled lipid droplets with high curvature act as stiff inclusions that disrupt the lamina, rupture the nucleus and increase DNA damage

The nucleus in many cell types is a stiff organelle, and yet fat-filled lipid droplets (FD's) in the cytoplasm can indent and displace the nucleus. FD's are phase-separated liquids with a poorly understood interfacial tension that determines how FD's interact with other organelles. Here, micron-sized FD's remain spherical while deforming both the nuclear lamina and peri-nuclear actomyosin. Nuclear lamins are intermediate filaments with a persistence length in the range of ∼0.2-1.5 μm with Lamin-B1 directly attached to the inner nuclear membrane via farnesylation groups that are lacking in mature lamin-A,C.