Mechanical and Aerospace Engineering Department, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Soft Matter. 2018 Jul 18;14(28):5741-5763. doi: 10.1039/c8sm00457a.
Locomotion of amoeboid cells is mediated by finger-like protrusions of the cell body, known as pseudopods, which grow, bifurcate, and retract in a dynamic fashion. Pseudopods are the primary mode of locomotion for many cells within the human body, such as leukocytes, embryonic cells, and metastatic cancer cells. Amoeboid motility is a complex and multiscale process, which involves bio-molecular reactions, cell deformation, and cytoplasmic and extracellular fluid motion. Additionally, cells within the human body are subject to a confined 3D environment known as the extra-cellular matrix (ECM), which resembles a fluid-filled porous medium. In this article, we present a 3D, multiphysics computational approach coupling fluid mechanics, solid mechanics, and a pattern formation model to simulate locomotion of amoeboid cells through a porous matrix composed of a viscous fluid and an array of finite-sized spherical obstacles. The model combines reaction-diffusion of activator/inhibitors, extreme deformation of the cell, pseudopod dynamics, cytoplasmic and extracellular fluid motion, and fully resolved extracellular matrix. A surface finite-element method is used to obtain the cell deformation and activator/inhibitor concentrations, while the fluid motion is solved using a combined finite-volume and spectral method. The immersed-boundary methods are used to couple the cell deformation, obstacles, and fluid. The model is able to recreate squeezing and weaving motion of cells through the matrix. We study the influence of matrix porosity, obstacle size, and cell deformability on the motility behavior. It is found that below certain values of these parameters, cell motion is completely inhibited. Phase diagrams are presented depicting such motility limits. Interesting dynamics seen in the presence of obstacles but absent in unconfined medium, such as freezing or cell arrest, probing, doubling-back, and tug-of-war are predicted. Furthermore, persistent unidirectional motion of cells that is often observed in an unconfined medium is shown to be lost in presence of obstacles, and is attributed to an alteration of the pseudopod dynamics. The same mechanism, however, allows the cell to find a new direction to penetrate further into the matrix without being stuck in one place. The results and analysis presented here show a strong coupling between cell deformability and ECM properties, and provide new fluid mechanical insights on amoeboid motility in confined medium.
变形虫细胞的运动是通过细胞体的指状突起（称为伪足）介导的，这些伪足以动态的方式生长、分叉和缩回。伪足是人体许多细胞的主要运动方式，如白细胞、胚胎细胞和转移性癌细胞。阿米巴样运动是一个复杂的多尺度过程，涉及生物分子反应、细胞变形以及细胞质和细胞外液的流动。此外，人体细胞处于一个受限的 3D 环境中，称为细胞外基质（ECM），它类似于充满流体的多孔介质。在本文中，我们提出了一种 3D 多物理计算方法，该方法将流体力学、固体力学和模式形成模型相结合，模拟变形虫细胞通过由粘性流体和一系列有限大小的球形障碍物组成的多孔基质的运动。该模型结合了激活剂/抑制剂的反应扩散、细胞的极端变形、伪足动力学、细胞质和细胞外液的流动以及完全解析的细胞外基质。表面有限元法用于获得细胞变形和激活剂/抑制剂浓度，而流体运动则使用组合的有限体积和谱方法求解。浸入边界法用于耦合细胞变形、障碍物和流体。该模型能够再现细胞通过基质的挤压和编织运动。我们研究了基质孔隙率、障碍物大小和细胞可变形性对运动行为的影响。结果发现，在这些参数的某些值以下，细胞运动完全受到抑制。呈现了描绘这种运动限制的相图。预测了在障碍物存在时会出现而在无约束介质中不存在的有趣动力学，例如冻结或细胞停滞、探测、折返和拔河。此外，在无约束介质中经常观察到的细胞持续单向运动在存在障碍物时会丢失，这归因于伪足动力学的改变。然而，相同的机制允许细胞在不被卡住的情况下找到新的方向进一步穿透基质。这里呈现的结果和分析表明细胞可变形性和 ECM 特性之间存在很强的耦合，并为受限介质中阿米巴样运动提供了新的流体力学见解。
