我们对流体力如何影响有限环境中细胞迁移的理解仍然有限。通过将微流体与活细胞成像相结合，我们证明了紧密但非中等限制空间中的细胞在受到流体力时会反转方向并向上游移动。当细胞表现出机械敏感性减弱、液压阻力升高或感知化学梯度时，这种流体力引起的方向变化发生的频率就会降低。正如数学和实验所示，细胞逆转需要肌动蛋白聚合到新的细胞前沿。肌动蛋白聚合对于 NHE1 的流体力诱导激活是必要的，NHE1 与钙配合诱导上游迁移。下游钙水平增加，反映了肌球蛋白 IIA 的亚细胞分布，其激活增强了上游迁移。核纤层蛋白 A/C 水平降低可防止细胞极性建立和细胞内钙升高，从而促进转移性肿瘤细胞的下​​游迁移。这种机制可以让癌细胞逃避高压环境，例如原发肿瘤。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Our understanding of how fluid forces influence cell migration in confining environments remains limited. By integrating microfluidics with live-cell imaging, we demonstrate that cells in tightly-but not moderately-confined spaces reverse direction and move upstream upon exposure to fluid forces. This fluid force-induced directional change occurs less frequently when cells display diminished mechanosensitivity, experience elevated hydraulic resistance, or sense a chemical gradient. Cell reversal requires actin polymerization to the new cell front, as shown mathematically and experimentally. Actin polymerization is necessary for the fluid force-induced activation of NHE1, which cooperates with calcium to induce upstream migration. Calcium levels increase downstream, mirroring the subcellular distribution of myosin IIA, whose activation enhances upstream migration. Reduced lamin A/C levels promote downstream migration of metastatic tumor cells by preventing cell polarity establishment and intracellular calcium rise. This mechanism could allow cancer cells to evade high-pressure environments, such as the primary tumor.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.