Chen Xiaoxiao, Xia Youjun, Du Wenqiang, Liu Han, Hou Ran, Song Yiyu, Xu Wenhu, Mao Yuxin, Chen Jianfeng
School of Advanced Manufacturing, Nanchang University, Nanchang, 330031 Jiangxi China.
Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, 230027 Anhui China.
Cell Mol Bioeng. 2023 May 1;16(3):205-218. doi: 10.1007/s12195-023-00766-y. eCollection 2023 Jun.
Cancer metastasis is associated with increased cancer incidence, recurrence, and mortality. The role of cell contact guidance behaviors in cancer metastasis has been recognized but has not been elucidated yet.
The contact guidance behavior of cancer cells in response to topographical constraints is identified using microgrooved substrates with varying dimensions at the mesoscopic scale. Then, the cell morphology is determined to quantitatively analyze the effects of substrate dimensions on cells contact guidance. Cell density and migrate velocity signatures within the cellular population are determined using time-lapse phase-contrast microscopy. The effect of soluble factors concentration is determined by culturing cells upside down. Then, the effect of cell-substrate interaction on cell migration is investigated using traction force microscopy.
With increasing depth and decreasing groove width, cell elongation and alignment are enhanced, while cell spreading is inhibited. Moreover, cells display preferential distribution on the ridges, which is found to be more pronounced with increasing depth and groove width. Determinations of cell density and migration velocity signatures reveal that the preferential distribution on ridges is caused by cell upward migration. Combined with traction force measurement, we find that migration toward ridges is governed by different cell-substrate interactions between grooves and ridges caused by geometrical constraints. Interestingly, the upward migration of cells at the mesoscopic scale is driven by entropic maximization.
The mesoscopic cell contact guidance mechanism based on the entropic force driven theory provides basic support for the study of cell alignment and migration along healthy tissues with varying size, thereby aiding in the prediction of cancer metastasis.
The online version contains supplementary material available at 10.1007/s12195-023-00766-y.
癌症转移与癌症发病率、复发率和死亡率的增加有关。细胞接触导向行为在癌症转移中的作用已得到认可，但尚未阐明。
使用介观尺度下具有不同尺寸的微槽基板来识别癌细胞对地形限制的接触导向行为。然后，确定细胞形态以定量分析基板尺寸对细胞接触导向的影响。使用延时相差显微镜确定细胞群体内的细胞密度和迁移速度特征。通过倒置培养细胞来确定可溶性因子浓度的影响。然后，使用牵引力显微镜研究细胞 - 基板相互作用对细胞迁移的影响。
随着深度增加和槽宽减小，细胞伸长和排列增强，而细胞铺展受到抑制。此外，细胞在脊上显示出优先分布，发现随着深度和槽宽增加这种分布更为明显。细胞密度和迁移速度特征的测定表明，脊上的优先分布是由细胞向上迁移引起的。结合牵引力测量，我们发现向脊的迁移受几何约束导致的槽和脊之间不同的细胞 - 基板相互作用控制。有趣的是，介观尺度下细胞的向上迁移是由熵最大化驱动的。
基于熵力驱动理论的介观细胞接触导向机制为研究细胞沿不同大小的健康组织排列和迁移提供了基础支持，从而有助于预测癌症转移。
在线版本包含可在10.1007/s12195 - 023 - 00766 - y获取的补充材料。
