Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Institute of NanoBioTechnology (INBT), Johns Hopkins University, Baltimore, MD, USA.
Adv Sci (Weinh). 2022 Oct;9(29):e2200927. doi: 10.1002/advs.202200927. Epub 2022 Aug 28.
Cells migrating in vivo encounter microenvironments with varying physical properties. One such physical variable is the fluid viscosity surrounding the cell. Increased viscosity is expected to increase the hydraulic resistance experienced by the cell and decrease cell speed. The authors demonstrate that contrary to this expected result, cells migrate faster in high viscosity media on 2-dimensional substrates. Both actin dynamics and water dynamics driven by ion channel activity are examined. Results show that cells increase in area in high viscosity and actomyosin dynamics remain similar. Inhibiting ion channel fluxes in high viscosity media results in a large reduction in cell speed, suggesting that water flux contributes to the observed speed increase. Moreover, inhibiting actin-dependent vesicular trafficking that transports ion channels to the cell boundary changes ion channel spatial positioning and reduces cell speed in high viscosity media. Cells also display altered Ca activity in high viscosity media, and when cytoplasmic Ca is sequestered, cell speed reduction and altered ion channel positioning are observed. Taken together, it is found that the cytoplasmic actin-phase and water-phase are coupled to drive cell migration in high viscosity media, in agreement with physical modeling that also predicts the observed cell speedup in high viscosity environments.
细胞在体内迁移时会遇到具有不同物理特性的微环境。其中一个物理变量是围绕细胞的流体粘度。人们预计,粘度的增加会增加细胞所经历的液压阻力,并降低细胞的速度。作者证明,与这一预期结果相反,细胞在二维基质上的高粘度介质中迁移得更快。研究了由离子通道活性驱动的肌动球蛋白动力学和水动力学。结果表明,细胞在高粘度下面积增大,肌动球蛋白动力学保持相似。在高粘度介质中抑制离子通道通量会导致细胞速度大幅降低,这表明水通量有助于观察到的速度增加。此外,抑制将离子通道运输到细胞边界的肌动蛋白依赖性囊泡运输会改变离子通道的空间定位,并降低高粘度介质中的细胞速度。细胞在高粘度介质中还显示出改变的 Ca 活性,并且当细胞质 Ca 被隔离时,观察到细胞速度降低和离子通道定位改变。总之,发现细胞质肌动球蛋白相和水相耦合以在高粘度介质中驱动细胞迁移,这与物理模型一致,该模型也预测了在高粘度环境中观察到的细胞加速。
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