Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation
Cell monolayers sense curvature by exploiting active mechanics and nuclear mechanoadaptation
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DOI：
10.1038/s41567-021-01374-1
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发表时间：
2021-11-18
期刊：
影响因子：
19.6
通讯作者：
Gabriele, Sylvain
中科院分区：
文献类型：
--
作者：
Luciano, Marine;Xue, Shi-Lei;Gabriele, Sylvain
许多生物体的早期发育都涉及细胞单层的折叠，但这种行为很难在体外重现；因此，局部曲率的机械原因和影响仍不清楚。在这里，我们研究了被设计成波浪图案的波纹水凝胶上的上皮细胞单层，研究凹曲率和凸曲率如何影响细胞和核形状。我们发现基底曲率影响单层厚度，山谷中的单层厚度大于峰顶。我们表明，这一特征通常出现在顶点模型中，从而得出这样的假设：细胞可以通过改变组织的厚度来感知曲率。我们发现局部曲率也会影响核形态和定位，我们通过扩展顶点模型以考虑膜-核相互作用，编码核变形和位置变化中的厚度调制来解释这一点。我们提出曲率通过核形状和密度变化来控制 yes 相关蛋白的空间分布。我们发现，曲率还会引起折叠上皮组织中核纤层、染色质浓缩和细胞增殖率的显着变化。总之，这项工作确定了活性细胞力学和核机械适应是上皮细胞对基质曲率机械调节的关键因素。波纹水凝胶上的细胞单层实验揭示了局部曲率对细胞和细胞核形状的影响。顶点模型支持了组织厚度的调制可以实现曲率感测的想法。
The early development of many organisms involves the folding of cell monolayers, but this behaviour is difficult to reproduce in vitro; therefore, both mechanistic causes and effects of local curvature remain unclear. Here we study epithelial cell monolayers on corrugated hydrogels engineered into wavy patterns, examining how concave and convex curvatures affect cellular and nuclear shape. We find that substrate curvature affects monolayer thickness, which is larger in valleys than crests. We show that this feature generically arises in a vertex model, leading to the hypothesis that cells may sense curvature by modifying the thickness of the tissue. We find that local curvature also affects nuclear morphology and positioning, which we explain by extending the vertex model to take into account membrane-nucleus interactions, encoding thickness modulation in changes to nuclear deformation and position. We propose that curvature governs the spatial distribution of yes-associated proteins via nuclear shape and density changes. We show that curvature also induces significant variations in lamins, chromatin condensation and cell proliferation rate in folded epithelial tissues. Together, this work identifies active cell mechanics and nuclear mechanoadaptation as the key players of the mechanistic regulation of epithelia to substrate curvature.Experiments on cell monolayers on corrugated hydrogels reveal the effects of local curvature on the shape of cells and nuclei. A vertex model lends support to the idea that the modulation of tissue thickness may enable curvature sensing.