Institute for Systems and Robotics - Lisboa and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
Molecular Biophysics and Structural Biology, University of Pittsburgh and Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
Cytoskeleton (Hoboken). 2021 Jun;78(6):277-283. doi: 10.1002/cm.21660. Epub 2021 Apr 22.
Force transmission throughout a monolayer is the result of complex interactions between cells. Monolayer adaptation to force imbalances such as singular stiffened cells provides insight into the initiation of disease and fibrosis. Here, NRK-52E cells transfected with ∆50LA, which significantly stiffens the nucleus. These stiffened cells were sparsely placed in a monolayer of normal NRK-52E cells. Through morphometric analysis and temporal tracking, the impact of the singular stiffened cells shows a pivotal role in mechanoresponse of the monolayer. A method for a detailed analysis of the spatial aspect and temporal progression of the nuclear boundary was developed and used to achieve a full description of the phenotype and dynamics of the monolayers under study. Our findings reveal that cells are highly sensitive to the presence of mechanically impaired neighbors, leading to generalized loss of coordination in collective cell migration, but without seemingly affecting the potential for nuclear lamina fluctuations of neighboring cells. Reduced translocation in neighboring cells appears to be compensated by an increase in nuclear rotation and dynamic variation of shape, suggesting a "frustration" of cells and maintenance of motor activity. Interestingly, some characteristics of the behavior of these cells appear to be dependent on the distance to a ∆50LA cell, pointing to compensatory behavior in response to force transmission imbalances in a monolayer. These insights may suggest the long-range impacts of single cell defects related to tissue dysfunction.
力在单层中的传递是细胞之间复杂相互作用的结果。单层对力失衡（如单个僵硬细胞）的适应提供了对疾病和纤维化起始的深入了解。在这里，NRK-52E 细胞转染了 ∆50LA，这显著地使核变硬。这些僵硬的细胞稀疏地分布在正常 NRK-52E 细胞的单层中。通过形态计量分析和时间追踪，单个僵硬细胞的影响表明其在单层的力反应中起着关键作用。开发了一种用于详细分析核边界空间方面和时间进展的方法，并用于对研究中的单层的表型和动力学进行全面描述。我们的发现表明，细胞对机械损伤的邻居的存在非常敏感，导致集体细胞迁移的协调普遍丧失，但似乎不影响相邻细胞核层流的潜力。相邻细胞中迁移的减少似乎被核旋转和形状的动态变化所补偿，这表明细胞的“受挫”和运动活性的维持。有趣的是，这些细胞行为的一些特征似乎取决于与 ∆50LA 细胞的距离，这表明对单层中力传递失衡的补偿行为。这些见解可能表明与组织功能障碍相关的单个细胞缺陷的远程影响。
