Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix

Macrophage (M phi)-fibroblast interactions coordinate tissue repair after injury whereas mis-communications can result in pathological healing and fibrosis. We show that contracting fibroblasts generate deformation fields in fibrillar collagen matrix that provide far-reaching physical cues for M phi. Within collagen deformation fields created by fibroblasts or actuated microneedles, M phi migrate towards the force source from several hundreds of micrometers away. The presence of a dynamic force source in the matrix is critical to initiate and direct M phi migration. In contrast, collagen condensation and fiber alignment resulting from fibroblast remodelling activities or chemotactic signals are neither required nor sufficient to guide M phi migration. Binding of alpha 2 beta 1 integrin and stretch-activated channels mediate M phi migration and mechanosensing in fibrillar collagen ECM. We propose that M phi mechanosense the velocity of local displacements of their substrate, allowing contractile fibroblasts to attract M phi over distances that exceed the range of chemotactic gradients.