Multiscale mechanobiology: Coupling models of adhesion kinetics and nonlinear tissue mechanics
Multiscale mechanobiology: Coupling models of adhesion kinetics and nonlinear tissue mechanics
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DOI：
10.1016/j.bpj.2022.01.012
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发表时间：
2022-02-15
影响因子：
3.4
通讯作者：
Tepole, Adrian Buganza
中科院分区：
文献类型：
--
作者：
Guo, Yifan;Calve, Sarah;Tepole, Adrian Buganza
宏观尺度下组织的力学行为与微观尺度下的细胞活动紧密耦合。皮肤伤口愈合是多尺度力学调节组织形式和功能恢复的复杂系统的一个突出例子。在皮肤伤口愈合中，纤维蛋白基质由从主要由胶原蛋白制成的周围组织迁移进来的成纤维细胞填充。成纤维细胞既响应机械信号，如纤维排列和刚度，也施加伤口闭合所需的主动应力。在这里，我们开发了一个多尺度模型与微观细胞粘附模型和宏观组织力学模型之间的双向耦合。从贝尔提出的著名的粘附动力学模型开始，我们扩展了配方，以解释纤维蛋白和胶原蛋白的非线性力学，并显示这种非线性响应如何自然地捕获拉伸驱动的机械传感。然后，我们将新的非线性粘附模型嵌入到组织力学平衡的自定义有限元实现中。在组织水平上的应变和应力与有限元网格的每个积分点处的微尺度粘附模型的解耦合。此外，粘附模型的解与细胞群的主动收缩应力相耦合。多尺度模型成功地捕获了生物聚合物纤维和凝胶的机械响应，成纤维细胞产生的收缩应力，以及伤口愈合过程中观察到的应力-应变轮廓。我们预计，这一框架将不仅增加我们的理解如何机械线索引导细胞行为在皮肤伤口愈合，但也将有助于在其他组织的机械生物学，生长和重塑的研究。
The mechanical behavior of tissues at the macroscale is tightly coupled to cellular activity at the microscale. Dermal wound healing is a prominent example of a complex system in which multiscale mechanics regulate restoration of tissue form and function. In cutaneous wound healing, a fibrin matrix is populated by fibroblasts migrating in from a surrounding tissue made mostly out of collagen. Fibroblasts both respond to mechanical cues, such as fiber alignment and stiffness, as well as exert active stresses needed for wound closure. Here, we develop a multiscale model with a two-way coupling between a microscale cell adhesion model and a macroscale tissue mechanics model. Starting from the well-known model of adhesion kinetics proposed by Bell, we extend the formulation to account for nonlinear mechanics of fibrin and collagen and show how this nonlinear response naturally captures stretch-driven mechanosensing. We then embed the new nonlinear adhesion model into a custom finite element implementation of tissue mechanical equilibrium. Strains and stresses at the tissue level are coupled with the solution of the microscale adhesion model at each integration point of the finite element mesh. In addition, solution of the adhesion model is coupled with the active contractile stress of the cell population. The multiscale model successfully captures the mechanical response of biopolymer fibers and gels, contractile stresses generated by fibroblasts, and stress-strain contours observed during wound healing. We anticipate that this framework will not only increase our understanding of how mechanical cues guide cellular behavior in cutaneous wound healing, but will also be helpful in the study of mechanobiology, growth, and remodeling in other tissues.