Microconstriction Arrays for High-Throughput Quantitative Measurements of Cell Mechanical Properties

Microconstriction Arrays for High-Throughput Quantitative Measurements of Cell Mechanical Properties
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DOI:
10.1016/j.bpj.2015.05.029
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发表时间:
2015-07-07
影响因子:
3.4
通讯作者:
Fabry, Ben
Fabry, Ben
中科院分区:
生物学3区
文献类型:
--
作者:
Lange, Janina R.;Steinwachs, Julian;Fabry, Ben

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我们描述了一种方法,用于定量的机械性能的细胞悬浮液与微流控装置组成的平行阵列的微米尺寸的收缩。使用高速电荷耦合器件相机,我们测量流速,细胞变形,并进入收缩的几百个细胞,每分钟通过该设备的过程中的时间。根据细胞的流速和微收缩阵列的占据状态,连续计算每个收缩的驱动压力。细胞进入微收缩的时间随着驱动压力的增加和细胞尺寸的减小而减小,并遵循幂律。根据这种幂律关系,可以估计细胞的弹性和流动性。当细胞用药物处理,使细胞骨架或细胞核稳定时,所有处理的弹性和流动性数据都会塌陷到一条主曲线上。幂律流变学和塌陷到主曲线上是由软玻璃质材料的理论预测的,并且先前已被证明可以描述粘附到基底上的细胞的机械行为。我们的发现,这一理论也适用于悬浮液中的细胞提供了一个定量的高通量测量的细胞机械性能与微流控装置的基础。
We describe a method for quantifying the mechanical properties of cells in suspension with a microfluidic device consisting of a parallel array of micron-sized constrictions. Using a high-speed charge-coupled device camera, we measure the flow speed, cell deformation, and entry time into the constrictions of several hundred cells per minute during their passage through the device. From the flow speed and the occupation state of the microconstriction array with cells, the driving pressure across each constriction is continuously computed. Cell entry times into microconstrictions decrease with increased driving pressure and decreased cell size according to a power law. From this power-law relationship, the cell elasticity and fluidity can be estimated. When cells are treated with drugs that depolymerize or stabilize the cytoskeleton or the nucleus, elasticity and fluidity data from all treatments collapse onto a master curve. Power-law rheology and collapse onto a master curve are predicted by the theory of soft glassy materials and have been previously shown to describe the mechanical behavior of cells adhering to a substrate. Our finding that this theory also applies to cells in suspension provides the foundation for a quantitative high-throughput measurement of cell mechanical properties with microfluidic devices.