The Nucleus Bypasses Obstacles by Deforming Like a Drop with Surface Tension Mediated by Lamin A/C.
The Nucleus Bypasses Obstacles by Deforming Like a Drop with Surface Tension Mediated by Lamin A/C.
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细胞核通过像滴度的液滴一样变形，绕过障碍物，与层固定蛋白A/C介导的表面张力。
DOI：
10.1002/advs.202201248
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发表时间：
2022-08
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迁移的细胞必须使它们坚硬的细胞核变形，才能穿过组织中的孔隙和纤维。已知核纤层蛋白A/C通过限制核变形和通过限制通道来阻碍细胞迁移，但其在核变形和通过纤维环境中的作用尚不清楚。细胞和核迁移通过离散的，紧密间隔的，细长的障碍，模仿胶原纤维的机械性能进行了研究。原子核绕过细长的障碍物，同时通过在它们周围变形而保持它们的整体形态，具有很小阻力的深局部内陷。这些障碍物不会阻碍核轨迹，也不会导致核膜破裂。在3D胶原蛋白凝胶中迁移的细胞中，细胞核同样在单个胶原蛋白纤维周围变形。与其在核通过限制通道中的限制作用相反，核纤层蛋白A/C促进核变形和通过纤维环境;核纤层蛋白缺失（Lmna−/−）细胞中的核失去其整体形态并缠绕在障碍物上。类似于表面张力介导的液滴变形，核纤层蛋白A/C赋予核表面张力，允许核内陷而几乎没有机械阻力，防止核缠结并允许核通过纤维环境。A）油滴在水中的形状是由细金属丝压成的。迁移细胞中的细胞核在围绕细而细长的胶原纤维B）或细长的微柱C）变形时呈液滴状。D）不规则变形的核缺乏核纤层蛋白A/C。这些数据表明，核变形像一个由核纤层A/C赋予表面张力的液滴。
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.