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一种用于模拟组织中细胞被动力学贡献的多尺度方法。

A multiscale approach to modeling the passive mechanical contribution of cells in tissues.

作者信息

Lai Victor K, Hadi Mohammad F, Tranquillo Robert T, Barocas Victor H

机构信息

Department of Chemical Engineering and Materials Science, University of Minnesota–Twin Cities, Minneapolis, MN 55455, USA.

出版信息

J Biomech Eng. 2013 Jul 1;135(7):71007. doi: 10.1115/1.4024350.

DOI:10.1115/1.4024350
PMID:23720192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3705800/
Abstract

In addition to their obvious biological roles in tissue function, cells often play a significant mechanical role through a combination of passive and active behaviors. This study focused on the passive mechanical contribution of cells in tissues by improving our multiscale model via the addition of cells, which were treated as dilute spherical inclusions. The first set of simulations considered a rigid cell, with the surrounding ECM modeled as (1) linear elastic, (2) Neo-Hookean, and (3) a fiber network. Comparison with the classical composite theory for rigid inclusions showed close agreement at low cell volume fraction. The fiber network case exhibited nonlinear stress-strain behavior and Poisson's ratios larger than the elastic limit of 0.5, characteristics similar to those of biological tissues. The second set of simulations used a fiber network for both the cell (simulating cytoskeletal filaments) and matrix, and investigated the effect of varying relative stiffness between the cell and matrix, as well as the effect of a cytoplasmic pressure to enforce incompressibility of the cell. Results showed that the ECM network exerted negligible compression on the cell, even when the stiffness of fibers in the network was increased relative to the cell. Introduction of a cytoplasmic pressure significantly increased the stresses in the cell filament network, and altered how the cell changed its shape under tension. Findings from this study have implications on understanding how cells interact with their surrounding ECM, as well as in the context of mechanosensation.

摘要

除了在组织功能中具有明显的生物学作用外,细胞还常常通过被动和主动行为的组合发挥重要的力学作用。本研究通过添加被视为稀疏散球形内含物的细胞来改进我们的多尺度模型,从而聚焦于细胞在组织中的被动力学贡献。第一组模拟考虑了一个刚性细胞,将周围的细胞外基质建模为:(1) 线性弹性的,(2) 新胡克弹性的,以及(3) 纤维网络。与刚性内含物的经典复合材料理论的比较表明,在低细胞体积分数下两者吻合度较高。纤维网络情况表现出非线性应力-应变行为,且泊松比大于弹性极限0.5,这些特征与生物组织相似。第二组模拟在细胞(模拟细胞骨架细丝)和基质中均使用了纤维网络,并研究了细胞与基质之间相对刚度变化的影响,以及细胞质压力对强制细胞不可压缩性的影响。结果表明,即使网络中纤维的刚度相对于细胞有所增加,细胞外基质网络对细胞施加的压缩也可忽略不计。引入细胞质压力显著增加了细胞细丝网络中的应力,并改变了细胞在张力下改变形状的方式。本研究的发现对于理解细胞如何与其周围的细胞外基质相互作用以及在机械传感背景下具有重要意义。

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