关键词: cell mechanics flow cytometry impedance signals intrinsic properties single-cell analysis

Mesh : Cell Line Elastic Modulus Electric Impedance Electrodes Humans Single-Cell Analysis / methods

来  源:   DOI:10.1002/smtd.202200325

Abstract:
Mechanical properties of single cells are important label-free biomarkers normally measured by expensive and complex imaging systems. To unlock this limit and allow mechanical properties comparable across different measurement platforms, camera-free intrinsic mechanical cytometry (CFIMC) is proposed for on-the-fly measurement of two major intrinsic mechanical parameters, that is, Young\'s modulus E and fluidity β, of single cells. CFIMC adopts a framework that couples the impedance electrodes with the constriction channel spatially, so that the impedance signals contain the dynamic deformability information of the cell squeezing through the constriction channel. Deformation of the cell is thus extracted from the impedance signals and used to derive the intrinsic mechanical parameters. With reasonably high throughput (>500 cells min-1 ), CFIMC can successfully reveal the mechanical difference in cancer and normal cells (i.e., human breast cell lines MCF-10A, MCF-7, and MDA-MB-231), living and fixed cells, and pharmacological perturbations of the cytoskeleton. It is further found that 1 µM level concentration of Cytochalasin B may be the threshold for the treated cells to induce a significant cytoskeleton effect reflected by the mechanical parameters. It is envisioned that CFIMC provides an alternative avenue for high-throughput and real-time single-cell intrinsic mechanical analysis.
摘要:
单细胞的机械特性是重要的无标记生物标志物,通常通过昂贵且复杂的成像系统测量。要解锁此限制并允许不同测量平台之间的机械性能具有可比性,提出了无相机固有力学细胞仪(CFMC),用于两个主要固有力学参数的动态测量,也就是说,杨氏模量E和流动性β,单细胞。CFMC采用将阻抗电极与收缩通道空间耦合的框架,使得阻抗信号包含细胞挤压通过收缩通道的动态变形性信息。因此,从阻抗信号中提取单元的变形,并用于导出固有机械参数。具有合理的高通量(>500个细胞min-1),CFMC可以成功揭示癌细胞和正常细胞的机械差异(即,人乳腺细胞系MCF-10A,MCF-7和MDA-MB-231),活的和固定的细胞,和细胞骨架的药理学扰动。进一步发现,1µM水平的细胞松弛素B浓度可能是经处理的细胞诱导力学参数反映的显着细胞骨架效应的阈值。设想CFIMC为高通量和实时单细胞固有机械分析提供了替代途径。
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