The Nucleus Bypasses Obstacles by Deforming Like a Drop with Surface Tension Mediated by Lamin A/C

• Published in: Advanced science Vol. 9; no. 23; pp. e2201248 - n/a
• Main Authors: Katiyar, Aditya, Zhang, Jian, Antani, Jyot D., Yu, Yifan, Scott, Kelsey L., Lele, Pushkar P., Reinhart‐King, Cynthia A., Sniadecki, Nathan J., Roux, Kyle J., Dickinson, Richard B., Lele, Tanmay P.
• Format: Journal Article
• Language: English
• Published: Weinheim John Wiley & Sons, Inc 01-08-2022; John Wiley and Sons Inc; Wiley
• Subjects: Cancer; cell mechanics; Collagen; confined cell migration; Deformation; Experiments; Extracellular matrix; Fibroblasts; microdevice; nuclear deformation; nuclear lamina; Silicon
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202201248

Migrating cells must deform their stiff cell nucleus to move through pores and fibers in tissue. Lamin A/C is known to hinder cell migration by limiting nuclear deformation and passage through confining channels, but its role in nuclear deformation and passage through fibrous environments is less clear. Cell and nuclear migration through discrete, closely spaced, slender obstacles which mimic the mechanical properties of collagen fibers are studied. Nuclei bypass slender obstacles while preserving their overall morphology by deforming around them with deep local invaginations of little resisting force. The obstacles do not impede the nuclear trajectory and do not cause rupture of the nuclear envelope. Nuclei likewise deform around single collagen fibers in cells migrating in 3D collagen gels. In contrast to its limiting role in nuclear passage through confining channels, lamin A/C facilitates nuclear deformation and passage through fibrous environments; nuclei in lamin‐null (Lmna−/−) cells lose their overall morphology and become entangled on the obstacles. Analogous to surface tension‐mediated deformation of a liquid drop, lamin A/C imparts a surface tension on the nucleus that allows nuclear invaginations with little mechanical resistance, preventing nuclear entanglement and allowing nuclear passage through fibrous environments.
A) Shape of an oil drop in water is indented by a slender wire. The nucleus in migrating cells takes drop‐like shapes when deforming around a thin, slender collagen fiber B) or a slender micropost C). D) The irregularly deformed nucleus lacks lamin A/C. These data suggest that the nucleus deforms like a drop with surface tension imparted by lamin A/C.