Guiding 3D cell migration in deformed synthetic hydrogel microstructures.

The ability of cells to navigate through the extracellular matrix, a network of biopolymers, is controlled by an interplay of cellular activity and mechanical network properties. Synthetic hydrogels with highly tuneable compositions and elastic properties are convenient model systems for the investigation of cell migration in 3D polymer networks. To study the impact of macroscopic deformations on single cell migration, we present a novel method to introduce uniaxial strain in matrices by microstructuring photo-polymerizable hydrogel strips with embedded cells in a channel slide. We find that such confined swelling results in a strained matrix in which cells exhibit an anisotropic migration response parallel to the strain direction. Surprisingly, however, the anisotropy of migration reaches a maximum at intermediate strain levels and decreases strongly at higher strains. We account for this non-monotonic response in the migration anisotropy with a computational model, in which we describe a cell performing durotactic and proteolytic migration in a deformable elastic meshwork. Our simulations reveal that the macroscopically applied strain induces a local geometric anisotropic stiffening of the matrix. This local anisotropic stiffening acts as a guidance cue for directed cell migration, resulting in a non-monotonic dependence on strain, as observed in our experiments. Our findings provide a mechanism for mechanical guidance that connects network properties on the cellular scale to cell migration behaviour.