发表机构
Université Côte d’Azur; CNRS, Laboratoire Jean-Alexandre Dieudonné; Université Paris Cité; CNRS, Epigenetics and Cell Fate; University of British Columbia; University of Zimbabwe; University of Pretoria; University of Johannesburg; Institut Universitaire de France（蔚蓝海岸大学; 法国国家科学研究中心让·亚历山大·迪厄多内实验室; 巴黎西岱大学; 法国国家科学研究中心表观遗传与细胞命运研究组; 不列颠哥伦比亚大学; 津巴布韦大学; 比勒陀利亚大学; 约翰内斯堡大学; 法兰西学院）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
本研究提出耦合几何表面与表面反应-扩散的二维框架，模拟受限细胞迁移中核力学，应用于肺癌细胞模型，再现SETDB1敲除导致的核力学变化及进入时间增加趋势。
AI 中文摘要
受限细胞迁移受核与细胞变形调控。在本工作中，我们构建了一个二维数学框架，其中细胞膜和核膜被表示为受表面张力、弯曲弹性和外部机械相互作用影响的力平衡定律所支配的演化闭合曲面。核力学依赖于多种因素，包括染色质组织和压实，这些受表观遗传修饰调控。核周边的分子调控由定义在演化核表面上的表面反应-扩散系统描述。我们将该耦合框架应用于一个实验表征的肺癌细胞模型，其中酶SETDB1和SUV39H1之间的平衡调控H3K9me3的周边沉积。利用实验测量的力学参数，我们表征了对照（Ctrl）和SETDB1敲除（SETDB1 KO）条件，这两种条件显示出不同的H3K9me3分布，尤其是在核周边。使用演化曲面有限元方法获得的数值解定性地再现了核力学的变化，以及实验观察到的SETDB1 KO细胞进入时间增加的部分现象。因此，该模型再现了实验观察的方向，而模拟与测量的进入时间之间的残余差异表明细胞响应是多因素的。
英文摘要
Confined cell migration is governed by nuclear and cellular deformation. In this work, we formulate a two-dimensional mathematical framework in which the cell and nuclear membranes are represented as evolving closed surfaces governed by force-balance laws incorporating surface tension, bending elasticity, and external mechanical interactions. Nuclear mechanics depends on several factors, including chromatin organization and compaction, which are regulated by epigenetic modifications. Molecular regulation at the nuclear periphery is described by a surface reaction-diffusion system posed on the evolving nuclear surface. We apply this coupled framework to an experimentally characterized lung cancer cell model in which the balance between the enzymes SETDB1 and SUV39H1 regulates the peripheral deposition of H3K9me3. Using experimentally measured mechanical parameters, we represent control (Ctrl) and SETDB1 knockout (SETDB1 KO) conditions, which display distinct H3K9me3 distributions, especially at the nuclear periphery. Numerical solutions obtained using the evolving surface finite element method qualitatively reproduce the changes in nuclear mechanics as well as part of the experimentally observed increase in the entry time in SETDB1 KO cells. The model therefore reproduces the direction of the experimental observations, while the residual difference between simulated and measured entry times indicates that the cellular response is multifactorial.
