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利用剪切流变形细胞术测量悬浮细胞的粘弹性特性。

Viscoelastic properties of suspended cells measured with shear flow deformation cytometry.

机构信息

Department of Physics, Friedrich-Alexander University Erlangen-Nurnberg, Erlangen, Germany.

Department of Physics and Astronomy, York-University Toronto, Ontario, Canada.

出版信息

Elife. 2022 Sep 2;11:e78823. doi: 10.7554/eLife.78823.

Abstract

Numerous cell functions are accompanied by phenotypic changes in viscoelastic properties, and measuring them can help elucidate higher level cellular functions in health and disease. We present a high-throughput, simple and low-cost microfluidic method for quantitatively measuring the elastic (storage) and viscous (loss) modulus of individual cells. Cells are suspended in a high-viscosity fluid and are pumped with high pressure through a 5.8 cm long and 200 µm wide microfluidic channel. The fluid shear stress induces large, ear ellipsoidal cell deformations. In addition, the flow profile in the channel causes the cells to rotate in a tank-treading manner. From the cell deformation and tank treading frequency, we extract the frequency-dependent viscoelastic cell properties based on a theoretical framework developed by R. Roscoe [1] that describes the deformation of a viscoelastic sphere in a viscous fluid under steady laminar flow. We confirm the accuracy of the method using atomic force microscopy-calibrated polyacrylamide beads and cells. Our measurements demonstrate that suspended cells exhibit power-law, soft glassy rheological behavior that is cell-cycle-dependent and mediated by the physical interplay between the actin filament and intermediate filament networks.

摘要

许多细胞功能伴随着粘弹性性质的表型变化,测量这些性质可以帮助阐明健康和疾病状态下更高层次的细胞功能。我们提出了一种高通量、简单且低成本的微流控方法,用于定量测量单个细胞的弹性(储存)和粘性(损耗)模量。细胞悬浮在高粘度流体中,并在高压下通过 5.8 厘米长、200 微米宽的微流道泵送。流体剪切应力诱导大的、耳状椭圆形细胞变形。此外,通道中的流动形态导致细胞以坦克履带方式旋转。根据 R. Roscoe [1] 开发的理论框架,我们从细胞变形和坦克履带频率中提取出频率相关的粘弹性细胞特性,该框架描述了在稳态层流粘性流体中粘弹性球体的变形。我们使用原子力显微镜校准的聚丙烯酰胺珠和细胞验证了该方法的准确性。我们的测量结果表明,悬浮细胞表现出幂律、软玻璃状流变行为,这种行为与肌动蛋白丝和中间丝网络之间的物理相互作用有关,并受细胞周期调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3fd/9576269/0c0efe05fddc/elife-78823-fig1.jpg

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