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使用受限微通道对生物细胞进行机械表型分析的实验与理论相结合的方法。

A combined experimental and theoretical approach towards mechanophenotyping of biological cells using a constricted microchannel.

机构信息

Department of Mechanical Engineering, Indian Institute of Technology Madras, Chennai-600036, India.

出版信息

Lab Chip. 2017 Oct 25;17(21):3704-3716. doi: 10.1039/c7lc00599g.

Abstract

We report a combined experimental and theoretical technique that enables the characterization of various mechanical properties of biological cells. The cells were infused into a microfluidic device that comprises multiple parallel micro-constrictions to eliminate device clogging and facilitate characterization of cells of different sizes and types on a single device. The extension ratio λ and transit velocity U of the cells were measured using high-speed and high-resolution imaging which were then used in a theoretical model to predict the Young's modulus E = f(λ, U) of the cells. The predicted Young's modulus E values for three different cell lines (182 ± 34.74 Pa for MDA MB 231, 360 ± 75 Pa for MCF 10A and, 763 ± 93 Pa for HeLa) compare well with those reported in the literature from micropipette measurements and atomic force microscopy measurement within 10% and 15%, respectively. Also, the Young's modulus of MDA-MB-231 cells treated with 50 μM 4-hyrdroxyacetophenone (for localization of myosin II) for 30 min was found out to be 260 ± 52 Pa. The entry time t of cells into the micro-constrictions was predicted using the model and validated using experimentally measured data. The entry and transit behaviors of cells in the micro-constriction including cell deformation (extension ratio λ) and velocity U were experimentally measured and used to predict various cell properties such as the Young's modulus, cytoplasmic viscosity and induced hydrodynamic resistance of different types of cells. The proposed combined experimental and theoretical approach leads to a new paradigm for mechanophenotyping of biological cells.

摘要

我们报告了一种组合的实验和理论技术,使各种生物细胞的机械性能的表征成为可能。将细胞注入微流控装置中,该装置包含多个平行的微通道,以消除装置堵塞,并便于在单个装置上对不同大小和类型的细胞进行表征。使用高速和高分辨率成像测量细胞的延伸比λ和传输速度 U,然后将其用于理论模型中,以预测细胞的杨氏模量 E = f(λ,U)。对于三种不同的细胞系(MDA-MB-231 为 182 ± 34.74 Pa,MCF 10A 为 360 ± 75 Pa,HeLa 为 763 ± 93 Pa),预测的杨氏模量 E 值与文献中报道的微管测量和原子力显微镜测量的结果在 10%和 15%以内。此外,用 50 μM 4-羟基苯乙酮(用于肌球蛋白 II 的定位)处理 30 分钟的 MDA-MB-231 细胞的杨氏模量被发现为 260 ± 52 Pa。使用模型预测细胞进入微通道的时间 t,并使用实验测量的数据进行验证。使用实验测量的数据进行验证。实验测量了细胞在微通道中的进入和传输行为,包括细胞变形(延伸比λ)和速度 U,并用于预测不同类型细胞的各种细胞特性,如杨氏模量、细胞质粘度和诱导的不同类型细胞的流体动力阻力。提出的组合实验和理论方法为生物细胞的机械表型提供了一种新的范例。

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