Modeling cellular self-organization in strain-stiffening hydrogels

Abstract We derive a three-dimensional hydrogel model as a two-phase system of a fibre network and liquid solvent, where the nonlinear elastic network accounts for the strain-stiffening properties typically encountered in biological gels. We use this model to formulate free boundary value problems for a hydrogel layer that allows for swelling or contraction. We derive two-dimensional plain-strain and plain-stress approximations for thick and thin layers respectively, that are subject to external loads and serve as a minimal model for scaffolds for cell attachment and growth. For the collective evolution of the cells as they mechanically interact with the hydrogel layer, we couple it to an agent-based model that also accounts for the traction force exerted by each cell on the hydrogel sheet and other cells during migration. We develop a numerical algorithm for the coupled system and present results on the influence of strain-stiffening, layer geometry, external load and solvent in/outflux on the shape of the layers and on the cell patterns. In particular, we discuss alignment of cells and chain formation under varying conditions.