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bioRxiv · 10.1101/2022.09.01.506190

Small, fat-filled lipid droplets remain spherical as they indent a nucleus, dilute the lamina, and cause rupture

Ivanovska, I.·Tobin, M.·Dooling, L.·Discher, D.
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Abstract

The nucleus in many cell types is a stiff organelle, and yet fat-filled lipid droplets (FDs) in the cytoplasm can be seen to indent and displace the nucleus. FDs are phase-separated liquids with a poorly understood interfacial tension {gamma} that determines how FDs interact with other organelles. Here, micron-sized FDs remain spherical as they indent both the nucleus and peri-nuclear actomyosin, dilute Lamin-B1 locally independent of Lamin-A,C, and trigger rupture with locally persistent accumulation in the nucleus of cGAS, a cytosolic DNA sensor. FD-nucleus interactions initiate rapid mis-localization of the essential DNA repair factor KU80, and nuclear rupture associates with DNA damage and perturbed cell cycle. Similar results are evident in FD-laden cells after constricted 3D-migration, which is impeded by FDs. Spherical shapes of small FDs are consistent with a high {gamma} that we measure for FDs mechanically isolated from fresh adipose tissue as [~]40_mN/m - which is far higher than other liquid condensates, but typical of oils in water and sufficiently rigid to disrupt cell structures.

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Ivanovska, I., Tobin, M., Dooling, L., Discher, D.. 2022-09-02. Small, fat-filled lipid droplets remain spherical as they indent a nucleus, dilute the lamina, and cause rupture. https://doi.org/10.1101/2022.09.01.506190

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