核力学调控细胞非拥堵化的时间动态
Nuclear mechanics controls the temporal dynamics of cell unjamming
AI总结：
本研究构建含可变形细胞核的汇合细胞计算模型，揭示核大小形状调控细胞非拥堵化转变，调和两类机制矛盾，其预测关系经两种乳腺癌细胞实验验证，明确核力学与组织刚性转变的关联。
AI中文摘要：
致密组织中的细胞非拥堵化是胚胎发生和癌症转移过程中复杂却至关重要的过程。越来越多证据表明，核力学与密度效应在集体细胞非拥堵化中发挥关键作用。然而，最先进的基于细胞形状的理论未能纳入核与密度效应，而具有刚性细胞核的计算机模型与“伸长的细胞核促进非拥堵化”的实验观察结果不符。在此，我们引入了一个具有明确可变形细胞核的汇合细胞计算模型，以研究细胞非拥堵化的动态。我们的模拟显示，由核大小和形状调控的非拥堵化转变，调和了密度驱动与形状驱动机制的冲突理论。我们预测了细胞和核形状与集体细胞运动之间的普遍关系，并在MCF-10A和MDA-MB-436乳腺癌细胞的不同单层中得到了惊人准确的实验验证。我们的工作建立了核力学与组织尺度刚性转变之间的合理联系，凸显了细胞核在集体细胞非拥堵化中的关键作用。
英文摘要：
Cell unjamming in dense tissues is a complex but essential process in embryogenesis and cancer metastasis. Increasing evidence suggests that nuclear mechanics and density effects play a vital role in collective cell unjamming. However, state-of-the-art cell-shape-based theories fail to include nuclear and density effects, while computer models featuring rigid nuclei disagree with experimental observations of elongated nuclei promoting unjamming. Here, we introduce a computational model of confluent cells with explicitly deformable nuclei to study the dynamics of cell unjamming. Our simulations show an unjamming transition controlled by nuclear size and shape, reconciling conflicting theories of density-driven versus shape-driven mechanisms. We predict general relations connecting cellular and nuclear shape to collective cell motion, verified experimentally in distinct monolayers of MCF-10A and MDA-MB-436 breast cells, with striking accuracy. Our work establishes a rational connection between nuclear mechanics and tissue-scale rigidity transitions, highlighting the nucleus's key role in collective cell unjamming.
