Liang Hong, Wang Ya-Jun, Liu Yixin, Liu Wei, Liu Baohong, Liu Yan-Jun
Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Shanghai Key Laboratory of Medical Epigenetics, Shanghai Stomatological Hospital, Institutes of Biomedical Sciences, Department of Chemistry, Fudan University, Shanghai 200032, China.
Chem Biomed Imaging. 2024 May 10;2(7):481-489. doi: 10.1021/cbmi.4c00035. eCollection 2024 Jul 22.
Cells can adapt to diverse topographical substrates through contact guidance, which regulates the cellular and nuclear morphologies and functions. How adaptive deformation of the cell body and nucleus coordinates to protect genetic material within mechanical microenvironments remains poorly understood. In this study, we engineered micrometer-level narrow-spacing micropillars to mimic constricted extracellular topographies in vivo, enabling us to explore variances in the nuclear architecture, cytoskeleton distribution, and chromatin conformation. The results showed that the area and volume of cell nuclei were distinctly smaller on micropillar topography. Actin and vimentin densely encapsulated the micropillars surrounding the nucleus, effectively segregating it from the micropillars. Additionally, nucleo-cytoskeleton lamin A/C exhibited a polarized distribution at the protrusion of the deformed nuclei. Notably, the degree of heterochromatin was altered in response to significant nuclear deformation, leading to a downregulation trend in H3K9me3 expression. These findings suggest that mechanical constraints imposed by microtopography profoundly influence cell behaviors, providing insights into disease diagnosis and therapeutic interventions in vivo.
细胞可以通过接触导向适应各种地形底物，接触导向可调节细胞和细胞核的形态及功能。在机械微环境中，细胞体和细胞核的适应性变形如何协同作用以保护遗传物质，目前仍知之甚少。在本研究中，我们设计了微米级窄间距微柱，以模拟体内狭窄的细胞外地形，从而使我们能够探索核结构、细胞骨架分布和染色质构象的变化。结果表明，在微柱地形上，细胞核的面积和体积明显较小。肌动蛋白和波形蛋白紧密包裹着细胞核周围的微柱，有效地将细胞核与微柱隔离开来。此外，核细胞骨架层粘连蛋白A/C在变形细胞核的突出处呈现极化分布。值得注意的是，异染色质的程度因显著的核变形而改变，导致H3K9me3表达呈下调趋势。这些发现表明，微观地形施加的机械约束对细胞行为有深远影响，为体内疾病诊断和治疗干预提供了见解。
