Computational Modeling of Cell Adhesion and Movement Using a Continuum-Kinetics Approach

Abstract

Adhesion of leukocytes to substrate involves the coupling of disparate length and timescales between molecular mechanics and macroscopic transport, and existing models of cell adhesion do not use full cellular information. To address these challenges, a multiscale computational approach for studying the adhesion of a cell on a substrate is developed and assessed. The cellular level model consists of a continuum representation of the field equations and a moving boundary tracking capability to allow the cell to change its shape continuously. At the receptor-ligand level, a bond molecule is mechanically represented by a spring. Communication between the macro/micro- and nanoscale models is facilitated interactively during the computation. The computational model is assessed using an adherent cell, rolling and deforming along the vessel wall under imposed shear flows. Using this approach, we first confirm existing numerical and experimental results. In this study, the intracellular viscosity and interfacial tension are found to directly affect the rolling of a cell. Our results also show that the presence of a nucleus increases the bond lifetime, and decreases the cell rolling velocity. Furthermore, it is found that a cell with a larger diameter rolls faster, and decreases the bond lifetime. This study shows that cell rheological properties have significant effects on the adhesion process contrary to what has been hypothesized in most literature.

Dynamic states of cells adhering in shear flow: From slipping to rolling

“…A large modeling effort has also been spent on the role of cell deformability [23,24,25,26,27] and the interaction between multiple particles [27,28,29]. Here we focus on the case of moderate shear flow and small numbers of cells, when cell deformability and hydrodynamic interactions between cells are not relevant [22].…”

A Fluid-Cell Interaction and Adhesion Algorithm for Tissue Coating of Cardiovascular Implants

“…Mathematical models proposed so far to describe different events in cell adhesion are based on either the equilibrium concept [2] or the kinetics concept [6,12,23,25]. See [28] for a nice overview. In our work we follow the kinetics-based probabilistic Dynamic Adhesion Algorithm by Hammer et al [6,23,25] used to study leukocyte rolling and adhesion to the endothelium in Stokes flow.…”

“…In their algorithm, a cell is treated as a rigid ball and the kinetics of bond association and dissociation is modeled in a probabilistic fashion. There are computational models that include deformability of cells by using either the elastic ring model [13,14] or a compound drop model [28]. These are two-dimensional models for deformable cells with the kinetics of receptor-ligand bonds represented by deterministic relations.…”

A computational model of chemotaxis-based cell aggregation

“…These models define cells as independent, discrete units that can move in response to continuous forces and influences. This approach has found use in simulating multicellular pattern formation (Fleischer and Barr, 1994), studying the chemotactic motility of individual cells (Jabbarzadeh and Abrams, 2005;Palsson and Othmer, 2000) and the computational modeling of cell adhesion (N'Dri et al, 2003).…”