Characterizing deformability and surface friction of cancer cells
Characterizing deformability and surface friction of cancer cells
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DOI：
10.1073/pnas.1218806110
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发表时间：
2013-05-07
影响因子：
11.1
通讯作者：
Manalis, Scott R.
中科院分区：
文献类型：
--
作者：
Byun, Sangwon;Son, Sungmin;Manalis, Scott R.
癌细胞的转移需要穿过狭小的空间，这是由细胞的物理特性及其与密闭环境的相互作用促成的。目前已设计出多种微流体方法，通过测量细胞穿过收缩物所需的时间来模拟体外穿越。虽然细胞的通过时间预计取决于其变形能力，但现有方法的测量结果会受到细胞大小及其与通道壁摩擦特性的影响。在这里，我们引入了一种设备，可以精确测量：(i) 单个细胞的大小（由其浮力质量决定）；(ii) 细胞进入收缩微通道的速度（进入速度）；(iii) 细胞通过收缩通道时的速度（通过速度）。通过扰动细胞骨架来改变细胞的变形能力主要会改变细胞的进入速度，而通过固定收缩壁上的正电荷来改变表面摩擦力主要会改变细胞的通过速度，这表明这些参数可以让人了解影响每个细胞通过的因素。在考虑细胞浮力质量时，我们发现具有较高转移潜能的细胞比转移潜能较低的细胞表现出更快的进入速度。此外，我们还发现一些转移潜能较高的细胞类型在通过速度上的变化比预期的要大，这表明不仅变形能力增加，而且摩擦力减小可能是使侵袭性癌细胞有效挤压通过狭小空间的一个因素。
Metastasis requires the penetration of cancer cells through tight spaces, which is mediated by the physical properties of the cells as well as their interactions with the confined environment. Various microfluidic approaches have been devised to mimic traversal in vitro by measuring the time required for cells to pass through a constriction. Although a cell's passage time is expected to depend on its deformability, measurements from existing approaches are confounded by a cell's size and its frictional properties with the channel wall. Here, we introduce a device that enables the precise measurement of (i) the size of a single cell, given by its buoyant mass, (ii) the velocity of the cell entering a constricted microchannel (entry velocity), and (iii) the velocity of the cell as it transits through the constriction (transit velocity). Changing the deformability of the cell by perturbing its cytoskeleton primarily alters the entry velocity, whereas changing the surface friction by immobilizing positive charges on the constriction's walls primarily alters the transit velocity, indicating that these parameters can give insight into the factors affecting the passage of each cell. When accounting for cell buoyant mass, we find that cells possessing higher metastatic potential exhibit faster entry velocities than cells with lower metastatic potential. We additionally find that some cell types with higher metastatic potential exhibit greater than expected changes in transit velocities, suggesting that not only the increased deformability but reduced friction may be a factor in enabling invasive cancer cells to efficiently squeeze through tight spaces.