Numerical investigation of the role of intercellular interactions on collective epithelial cell migration

Abstract

During collective cell migration, the intercellular forces will significantly affect the collective migratory behaviors. However, the measurement of mechanical stresses exerted at cell-cell junctions is very challenging. A recent experimental observation indicated that the intercellular adhesion sites within a migrating monolayer are subjected to both normal stress exerted perpendicular to cell-cell junction surface and shear stress exerted tangent to cell-cell junction surface. In this study, an interfacial interaction model was proposed to model the intercellular interactions for the first time. The intercellular interaction model-based study of collective epithelial migration revealed that the direction of cell migration velocity has better alignment with the orientation of local principal stress at higher maximum shear stress locations in an epithelial monolayer sheet. Parametric study of the effects of adhesion strength indicated that normal adhesion strength at the cell-cell junction surface has dominated effect on local alignment between the direction of cell velocity vector and the principal stress orientation, while the shear adhesion strength has little effect, which provides compelling evidence to help explain the force transmission via cell-cell junctions between adjacent cells in collective cell motion and provides new insights into "adhesive belt" effects at cell-cell junction.

Computational Investigation of Cell Migration Behavior in a Confluent Epithelial Monolayer

“…Numerical simulations were performed to investigate the cell migration behavior in a confluent epithelial monolayer. All simulations were conducted by using a custom-designed finite element package using Fortran, which was developed by Lin et al [42].…”

“…These models incorporate the contribution of the intercellular adhesion, however, they are pure mathematical models that could not capture the mechanical behavior of the cell tissue. In this study, the intercellular interactions at cell-cell junctions were modeled using an interfacial interaction model which was proposed by Lin et al [42] to investigate the collective epithelial cell migration, and it takes the following forms:…”

“…3. This model has been employed to describe intercellular interactions in collective cell migration and in other biological material modelings [42,55].…”

“…The simulation studies implied that either cell crawling or purse-string contraction can lead to wound closure. Lin et al [42] proposed an interfacial interaction model to study the collective epithelial cell migration behavior. Through the simulation, it reveals that the direction of cell movement is better aligned with the local principal stress direction at the higher maximum shear stress region.…”

Computational modeling and simulation of epithelial wound closure

“…These models incorporate the contribution of cell cortical tension and particle-based intercellular adhesion, however, they are mathematical models that could not capture the mechanical behavior of the cell tissue and intercellular interaction at the cell–cell junction surface directly. In this study, the intercellular interactions at cell–cell junctions were modeled using an interfacial interaction model which was proposed by Lin et al to investigate the collective epithelial cell migration 41 , and it takes the following forms: …”