Tocco Vincent J, Li Yuan, Christopher Keith G, Matthews James H, Aggarwal Varun, Paschall Lauren, Luesch Hendrik, Licht Jonathan D, Dickinson Richard B, Lele Tanmay P
Department of Chemical Engineering, University of Florida, Gainesville, Florida.
Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, Gainesville, Florida.
J Cell Physiol. 2018 Feb;233(2):1446-1454. doi: 10.1002/jcp.26031. Epub 2017 Jul 31.
Actomyosin stress fibers impinge on the nucleus and can exert compressive forces on it. These compressive forces have been proposed to elongate nuclei in fibroblasts, and lead to abnormally shaped nuclei in cancer cells. In these models, the elongated or flattened nuclear shape is proposed to store elastic energy. However, we found that deformed shapes of nuclei are unchanged even after removal of the cell with micro-dissection, both for smooth, elongated nuclei in fibroblasts and abnormally shaped nuclei in breast cancer cells. The lack of shape relaxation implies that the nuclear shape in spread cells does not store any elastic energy, and the cellular stresses that deform the nucleus are dissipative, not static. During cell spreading, the deviation of the nucleus from a convex shape increased in MDA-MB-231 cancer cells, but decreased in MCF-10A cells. Tracking changes of nuclear and cellular shape on micropatterned substrata revealed that fibroblast nuclei deform only during deformations in cell shape and only in the direction of nearby moving cell boundaries. We propose that motion of cell boundaries exert a stress on the nucleus, which allows the nucleus to mimic cell shape. The lack of elastic energy in the nuclear shape suggests that nuclear shape changes in cells occur at constant surface area and volume.
肌动球蛋白应力纤维作用于细胞核，并可对其施加压缩力。有人提出，这些压缩力会使成纤维细胞中的细胞核伸长，并导致癌细胞中的细胞核形状异常。在这些模型中，细胞核伸长或扁平的形状被认为是储存了弹性能量。然而，我们发现，无论是成纤维细胞中光滑、细长的细胞核，还是乳腺癌细胞中形状异常的细胞核，即使在通过显微切割去除细胞后，细胞核的变形形状仍保持不变。形状缺乏松弛表明，铺展细胞中的细胞核形状不储存任何弹性能量，使细胞核变形的细胞应力是耗散性的，而非静态的。在细胞铺展过程中，MDA-MB-231癌细胞中细胞核偏离凸形的程度增加，而MCF-10A细胞中则减少。在微图案化基质上追踪细胞核和细胞形状的变化发现，成纤维细胞核仅在细胞形状变形期间且仅在附近移动的细胞边界方向上发生变形。我们提出，细胞边界的运动对细胞核施加了应力，这使得细胞核能够模仿细胞形状。细胞核形状中弹性能量的缺乏表明，细胞中细胞核形状的变化是在表面积和体积恒定的情况下发生的。
