Mechanical and Aerospace Engineering Department, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.
Biomech Model Mechanobiol. 2021 Feb;20(1):167-191. doi: 10.1007/s10237-020-01376-7. Epub 2020 Aug 9.
Amoeboid cells often migrate using pseudopods, which are membrane protrusions that grow, bifurcate, and retract dynamically, resulting in a net cell displacement. Many cells within the human body, such as immune cells, epithelial cells, and even metastatic cancer cells, can migrate using the amoeboid phenotype. Amoeboid motility is a complex and multiscale process, where cell deformation, biochemistry, and cytosolic and extracellular fluid motions are coupled. Furthermore, the extracellular matrix (ECM) provides a confined, complex, and heterogeneous environment for the cells to navigate through. Amoeboid cells can migrate without significantly remodeling the ECM using weak or no adhesion, instead utilizing their deformability and the microstructure of the ECM to gain enough traction. While a large volume of work exists on cell motility on 2D substrates, amoeboid motility is 3D in nature. Despite recent progress in modeling cellular motility in 3D, there is a lack of systematic evaluations of the role of ECM microstructure, cell deformability, and adhesion on 3D motility. To fill this knowledge gap, here we present a multiscale, multiphysics modeling study of amoeboid motility through 3D-idealized ECM. The model is a coupled fluid‒structure and coarse-grain biochemistry interaction model that accounts for large deformation of cells, pseudopod dynamics, cytoplasmic and extracellular fluid motion, stochastic dynamics of cell-ECM adhesion, and microstructural (pore-scale) geometric details of the ECM. The key finding of the study is that cell deformation and matrix porosity strongly influence amoeboid motility, while weak adhesion and microscale structural details of the ECM have secondary but subtle effects.
变形虫细胞通常使用伪足进行迁移，伪足是细胞膜的突起，能够动态地生长、分叉和回缩，从而导致细胞的净位移。人体内的许多细胞，如免疫细胞、上皮细胞，甚至转移性癌细胞，都可以使用变形虫表型进行迁移。变形虫运动是一个复杂的多尺度过程，其中细胞变形、生物化学以及细胞质和细胞外液的运动是耦合的。此外，细胞外基质（ECM）为细胞提供了一个受限的、复杂的和异质的环境，以便它们在其中导航。变形虫细胞可以在不显著重塑 ECM 的情况下进行迁移，使用弱或无黏附力，而是利用它们的可变形性和 ECM 的微观结构来获得足够的牵引力。尽管在二维基质上的细胞运动有大量的工作，但变形虫运动本质上是三维的。尽管最近在三维细胞运动建模方面取得了进展，但对于 ECM 微观结构、细胞可变形性和黏附对三维运动的作用，缺乏系统的评估。为了填补这一知识空白，我们在这里提出了一个多尺度、多物理的变形虫通过三维理想化 ECM 运动的建模研究。该模型是一个耦合的流体-结构和粗粒生物化学相互作用模型，考虑了细胞的大变形、伪足动力学、细胞质和细胞外液的流动、细胞-ECM 黏附的随机动力学以及 ECM 的微观结构（孔尺度）几何细节。研究的主要发现是细胞变形和基质孔隙度强烈影响变形虫运动，而弱黏附和 ECM 的微尺度结构细节则具有次要但微妙的影响。
