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迁移，伪足是动态生长、分叉和收缩的膜突起，导致细胞净位移。人体内的许多细胞，例如免疫细胞、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、生物化学以及细胞溶质和细胞外液运动相互耦合。此外，细胞外基质 (ECM) 为细胞提供了一个封闭、复杂和异质的环境。变形虫细胞可以在不使用弱粘附或无粘附显着重塑 ECM 的情况下迁移，而是利用它们的变形能力和 ECM 的微观结构来获得足够的牵引力。虽然在 2D 基质上存在大量关于细胞运动的工作，但变形虫运动本质上是 3D 的。尽管最近在 3D 中模拟细胞运动方面取得了进展，但缺乏对 ECM 微观结构、细胞变形性和粘附对 3D 运动的作用的系统评估。为了填补这一知识空白，我们在这里通过 3D 理想化 ECM 对变形虫运动进行了多尺度、多物理场建模研究。该模型是一个耦合流固耦合和粗粒生化相互作用模型，它解释了细胞的大变形、伪足动力学、细胞质和细胞外液运动、细胞-ECM 粘附的随机动力学以及微结构（孔尺度）几何细节。 ECM。该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，