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.

许多生物的早期发育涉及细胞单层的折叠，但这种行为在体外很难复制；因此，局部曲率的机制原因和影响仍不清楚。在这里，我们研究了设计成波浪形图案的波纹水凝胶上的上皮细胞单层，研究了凹凸曲率如何影响细胞和核形状。我们发现基板曲率影响单层厚度，其在谷中大于波峰。我们表明该特征通常出现在顶点模型中，从而导致细胞可以通过改变组织厚度来感知曲率的假设。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 - 核相互作用来解释这一点，在核变形和位置的变化中编码厚度调制。我们提出曲率通过核形状和密度变化来控制是相关蛋白的空间分布。我们表明，曲率还诱导折叠上皮组织中核纤层蛋白、染色质凝聚和细胞增殖率的显着变化。总之，这项工作将活性细胞力学和核力学适应确定为上皮细胞对底物曲率的机械调节的关键参与者。