State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University , Shanghai 200433, China.
ACS Appl Mater Interfaces. 2017 Jun 7;9(22):18521-18530. doi: 10.1021/acsami.7b04027. Epub 2017 May 25.
Cells respond to the mechanical signals from their surroundings and integrate physiochemical signals to initiate intricate mechanochemical processes. While many studies indicate that topological features of biomaterials impact cellular behaviors profoundly, little research has focused on the nuclear response to a mechanical force generated by a topological surface. Here, we fabricated a polymeric micropillar array with an appropriate dimension to induce a severe self-deformation of cell nuclei and investigated how the nuclear shape changed over time. Intriguingly, the nuclei of mesenchymal stem cells (MSCs) on the poly(lactide-co-glycolide) (PLGA) micropillars exhibited a significant initial deformation followed by a partial recovery, which led to an "overshoot" phenomenon. The treatment of cytochalasin D suppressed the recovery of nuclei, which indicated the involvement of actin cytoskeleton in regulating the recovery at the second stage of nuclear deformation. Additionally, we found that MSCs exhibited different overshoot extents from their differentiated lineage, osteoblasts. These findings enrich the understanding of the role of the cell nucleus in mechanotransduction. As the first quantitative report on nonmonotonic kinetic process of self-deformation of a cell organelle on biomaterials with unique topological surfaces, this study sheds new insight into cell-biomaterial interactions.
细胞对外界的机械信号做出反应，并整合物理化学信号，从而启动复杂的力-化学过程。尽管许多研究表明生物材料的拓扑特征会深刻影响细胞行为，但很少有研究关注拓扑表面产生的机械力对细胞核的响应。在这里，我们制造了具有适当尺寸的聚合物微柱阵列，以诱导细胞核发生严重的自变形，并研究了细胞核形状随时间的变化。有趣的是，间充质干细胞（MSCs）在聚（乳酸-共-乙醇酸）（PLGA）微柱上的细胞核表现出显著的初始变形，随后部分恢复，导致“过冲”现象。细胞松弛素 D 的处理抑制了细胞核的恢复，表明肌动蛋白细胞骨架参与调节细胞核变形的第二阶段的恢复。此外，我们发现 MSCs 从其分化谱系（成骨细胞）表现出不同的过冲程度。这些发现丰富了对细胞核在力转导中作用的理解。作为关于具有独特拓扑表面的生物材料中细胞细胞器自变形的非单调动力学过程的第一份定量报告，本研究为细胞-生物材料相互作用提供了新的见解。
