Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device
Measuring Cell Viscoelastic Properties Using a Microfluidic Extensional Flow Device
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DOI：
10.1016/j.bpj.2016.09.034
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发表时间：
2016-11-01
影响因子：
3.4
通讯作者：
Kumar, Sanjay
中科院分区：
文献类型：
--
作者：
Guillou, Lionel;Dahl, Joanna B.;Kumar, Sanjay
细胞力学性质的定量研究在生物学和医学领域具有重要意义。最近的微流控技术，推断细胞的机械性能的基础上分析的细胞变形在微通道穿越大大提高了吞吐量超过传统的单细胞流变学工具，但从这些测量提取的材料参数仍然相当复杂，由于挑战，如通道壁的限制和复杂的惯性力的支配。在这里，我们描述了一个简单的微流体平台，使用低雷诺数和低限制的水动力伸长单细胞附近的平面延伸流的停滞点。在串联，我们提出，据我们所知，一种新的分析框架，使确定细胞的粘弹性（刚度和流动性）从这些测量。我们通过测量交联葡聚糖微粒的刚度来验证我们的系统和分析，这与先前报道的值和我们的微量移液管抽吸测量值产生了合理的一致性。然后，我们测量了3T3成纤维细胞和胶质母细胞瘤肿瘤起始细胞的粘弹性。我们的系统捕获了预期的弹性模量的变化，在3T3成纤维细胞和肿瘤起始细胞中诱导，以响应软化（细胞松弛素D）或软化（多聚甲醛）细胞骨架的试剂。该设备的简单性加上我们的分析模型，可以直接测量细胞和柔软的球形物体的粘弹性。
The quantification of cellular mechanical properties is of tremendous interest in biology and medicine. Recent microfluidic technologies that infer cellular mechanical properties based on analysis of cellular deformations during microchannel traversal have dramatically improved throughput over traditional single-cell rheological tools, yet the extraction of material parameters from these measurements remains quite complex due to challenges such as confinement by channel walls and the domination of complex inertial forces. Here, we describe a simple microfluidic platform that uses hydrodynamic forces at low Reynolds number and low confinement to elongate single cells near the stagnation point of a planar extensional flow. In tandem, we present, to our knowledge, a novel analytical framework that enables determination of cellular viscoelastic properties (stiffness and fluidity) from these measurements. We validated our system and analysis by measuring the stiffness of cross-linked dextran microparticles, which yielded reasonable agreement with previously reported values and our micropipette aspiration measurements. We then measured viscoelastic properties of 3T3 fibroblasts and glioblastoma tumor initiating cells. Our system captures the expected changes in elastic modulus induced in 3T3 fibroblasts and tumor initiating cells in response to agents that soften (cytochalasin D) or stiffen (paraformaldehyde) the cytoskeleton. The simplicity of the device coupled with our analytical model allows straightforward measurement of the viscoelastic properties of cells and soft, spherical objects.