Carrasco-Mantis A, Alarcón T, Sanz-Herrera J A
Escuela Técnica Superior de Ingeniería, Universidad de Sevilla, Spain.
ICREA (Institució Catalana de Recerca i Estudis Avançats), Centre de Recerca Matemàtica, Barcelona, Spain.
Comput Methods Programs Biomed. 2023 Apr;231:107369. doi: 10.1016/j.cmpb.2023.107369. Epub 2023 Jan 27.
Blood vessels form a network of capillaries throughout the body that perform essential functions for life. Vasculogenesis, i.e. the formation of new blood vessels, is regulated by many factors, biochemical ones being among the most important. However, others such as the biomechanical influence on shape, organization and structure of vessel networks require further investigation. In this paper, we develop a 3D agent-based mechanobiological model of vasculogenesis with the aim of analyzing how the mechanics of the extracellular matrix (ECM) affects vasculogenesis.
For this purpose, we consider a growing domain composed of different cells: tip cells, which are the driving cells located at the end of the vessels and stalk cells, which are found in the interior of the vascular network. ECM is considered as particles (agents) that surround the growth of the vascular network. Depending on the cell type, different sets of forces are considered, such as chemotactic, mechanical, random and viscoelastic forces among others.
The growth of the network is iteratively analyzed and updated at each time step based on a mechanically-driven proliferation rule. The influence of different biomechanical factors, such as ECM stiffness or viscoelasticity are explored through in silico simulations. A number of indicators are defined along the algorithm, like number of cells, branches, tortuosity and anisotropy, in order to compare topological differences of the vascular network during vasculogenesis under different ECM conditions. The obtained results are qualitatively compared with other related works in the literature.
The present study sheds some light and partially explain, from an in silico perspective, the role of ECM mechanics on vasculogenesis. The main conclusions of this work are: (i) increased stiffness increases proliferation, (ii) the network tends to migrate towards stiffer areas, and (iii) increased viscoelasticity decreases proliferation.
血管在全身形成毛细血管网络，执行着维持生命的基本功能。血管生成，即新血管的形成，受多种因素调控，其中生化因素最为重要。然而，其他因素，如生物力学对血管网络形状、组织和结构的影响，仍需进一步研究。在本文中，我们开发了一种基于智能体的血管生成三维力学生物学模型，旨在分析细胞外基质（ECM）的力学特性如何影响血管生成。
为此，我们考虑一个由不同细胞组成的生长区域：位于血管末端的驱动细胞——尖端细胞，以及位于血管网络内部的柄细胞。ECM被视为围绕血管网络生长的粒子（智能体）。根据细胞类型，考虑不同的力集，如趋化力、机械力、随机力和粘弹力等。
基于机械驱动的增殖规则，在每个时间步对网络的生长进行迭代分析和更新。通过计算机模拟探索不同生物力学因素的影响，如ECM硬度或粘弹性。在算法中定义了一些指标，如细胞数量、分支数、曲折度和各向异性，以便比较不同ECM条件下血管生成过程中血管网络的拓扑差异。将所得结果与文献中其他相关研究进行定性比较。
本研究从计算机模拟的角度，对ECM力学在血管生成中的作用提供了一些见解并进行了部分解释。这项工作的主要结论是：（i）硬度增加会促进增殖；（ii）网络倾向于向更硬的区域迁移；（iii）粘弹性增加会降低增殖。
