Abstract

Endothelial cell monolayers line the inner surfaces of blood and lymphatic vessels. They are continuously exposed to different mechanical loads, which may trigger mechanobiological signals and hence play a role in both physiological and pathological processes. Computer-based mechanical models of cells contribute to a better understanding of the relation between cell-scale loads and cues and the mechanical state of the hosting tissue. However, the confluency of the endothelial monolayer complicates these approaches since the intercellular cross-talk needs to be accounted for in addition to the cytoskeletal mechanics of the individual cells themselves. As a consequence, the computational approach must be able to efficiently model a large number of cells and their interaction. Here, we simulate cytoskeletal mechanics by means of molecular dynamics software, generally suitable to deal with large, locally interacting systems. Methods were developed to generate models of single cells and large monolayers with hundreds of cells. The single-cell model was considered for a comparison with experimental data. To this end, we simulated cell interactions with a continuous, deformable substrate, and computationally replicated multistep traction force microscopy experiments on endothelial cells. The results indicate that cell discrete network models are able to capture relevant features of the mechanical behaviour and are thus well-suited to investigate the mechanics of the large cytoskeletal network of individual cells and cell monolayers.

中文翻译：

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内皮细胞的离散网络模型及其与基质的相互作用

摘要

内皮细胞单层排列在血管和淋巴管的内表面。它们持续承受不同的机械负荷，这可能会触发机械生物学信号，从而在生理和病理过程中发挥作用。基于计算机的细胞机械模型有助于更好地理解细胞尺度负载和线索与宿主组织机械状态之间的关系。然而，内皮单层的汇合使这些方法变得复杂，因为除了单个细胞本身的细胞骨架力学之外，还需要考虑细胞间串扰。因此，计算方法必须能够有效地模拟大量细胞及其相互作用。在这里，我们通过分子动力学软件模拟细胞骨架力学，通常适合处理大型局部相互作用系统。开发了生成单细胞和具有数百个细胞的大型单层模型的方法。考虑使用单细胞模型与实验数据进行比较。为此，我们模拟了细胞与连续、可变形基质的相互作用，并对内皮细胞进行了计算复制的多步牵引力显微镜实验。结果表明，细胞离散网络模型能够捕获机械行为的相关特征，因此非常适合研究单个细胞和单层细胞的大型细胞骨架网络的力学。