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微通道中癌细胞的瞬态流动诱导变形:通用计算模型与实验

Transient flow-induced deformation of cancer cells in microchannels: a general computational model and experiments.

作者信息

Lu R, Li J, Guo Z, Wang Z, Feng J J, Sui Y

机构信息

School of Engineering and Materials Science, Queen Mary University of London, London, E1 4NS, UK.

Departments of Mathematics and Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, V6T 1Z2, Canada.

出版信息

Biomech Model Mechanobiol. 2025 Apr;24(2):489-506. doi: 10.1007/s10237-024-01920-9. Epub 2025 Feb 2.

Abstract

Recently, the present authors proposed a three-dimensional computational model for the transit of suspended cancer cells through a microchannel (Wang et al. in Biomech Model Mechanobiol 22: 1129-1143, 2023). The cell model takes into account the three major subcellular components: A viscoelastic membrane that represents the lipid bilayer supported by the underlying cell cortex, a viscous cytoplasm, and a nucleus modelled as a smaller microcapsule. The cell deformation and its interaction with the surrounding fluid were solved by an immersed boundary-lattice Boltzmann method. The computational model accurately recovered the transient flow-induced deformation of the human leukaemia HL-60 cells in a constricted channel. However, as a general modelling framework, its applicability to other cell types in different flow geometries remains unknown, due to the lack of quantitative experimental data. In this study, we conduct experiments of the transit of human prostate cancer (PC-3) and leukaemia (K-562) cells, which represent solid and liquid tumour cell lines, respectively, through two distinct microchannel geometries, each dominated by shear and extension flow. We find that the two cell lines have qualitatively similar flow-induced dynamics. Comparisons between experiments and numerical simulations suggest that our model can accurately predict the transient cell deformation in both geometries, and that it can serve as a general modelling framework for the dynamics of suspended cancer cells in microchannels.

摘要

最近,本文作者提出了一种用于模拟悬浮癌细胞在微通道中传输的三维计算模型(Wang等人,《生物力学模型与分子生物学》,2023年,第22卷,第1129 - 1143页)。该细胞模型考虑了三个主要的亚细胞成分:一个代表由下层细胞皮层支撑的脂质双层的粘弹性膜、粘性的细胞质以及被建模为较小微胶囊的细胞核。通过浸入边界 - 格子玻尔兹曼方法求解细胞变形及其与周围流体的相互作用。该计算模型准确地再现了人白血病HL - 60细胞在狭窄通道中由流动引起的瞬态变形。然而,作为一个通用的建模框架,由于缺乏定量实验数据,其对不同流动几何形状下其他细胞类型的适用性仍然未知。在本研究中,我们进行了人前列腺癌(PC - 3)细胞和白血病(K - 562)细胞分别通过两种不同微通道几何形状的传输实验,这两种细胞系分别代表实体瘤和液体瘤细胞系,且每种微通道几何形状分别以剪切流和拉伸流为主导。我们发现这两种细胞系在流动诱导动力学方面具有定性相似性。实验与数值模拟之间的比较表明,我们的模型能够准确预测两种几何形状下细胞的瞬态变形,并且它可以作为微通道中悬浮癌细胞动力学的通用建模框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a6d/12055957/377ccbc4208d/10237_2024_1920_Fig1_HTML.jpg

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