Dynamic fibroblast contractions attract remote macrophages in fibrillar collagen matrix

Pardis Pakshir, Moien Alizadehgiashi, Boaz Wong, Nuno Miranda Coelho, Xingyu Chen, Ze Gong, Vivek B. Shenoy, Christopher A. McCulloch and Boris Hinz ()
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Pardis Pakshir: University of Toronto
Moien Alizadehgiashi: University of Toronto
Boaz Wong: University of Western Ontario
Nuno Miranda Coelho: University of Toronto
Xingyu Chen: University of Pennsylvania
Ze Gong: University of Pennsylvania
Vivek B. Shenoy: University of Pennsylvania
Christopher A. McCulloch: University of Toronto
Boris Hinz: University of Toronto

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract Macrophage (Mϕ)-fibroblast interactions coordinate tissue repair after injury whereas miscommunications 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 Mϕ. Within collagen deformation fields created by fibroblasts or actuated microneedles, Mϕ 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 Mϕ migration. In contrast, collagen condensation and fiber alignment resulting from fibroblast remodelling activities or chemotactic signals are neither required nor sufficient to guide Mϕ migration. Binding of α2β1 integrin and stretch-activated channels mediate Mϕ migration and mechanosensing in fibrillar collagen ECM. We propose that Mϕ mechanosense the velocity of local displacements of their substrate, allowing contractile fibroblasts to attract Mϕ over distances that exceed the range of chemotactic gradients.

Date: 2019
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DOI: 10.1038/s41467-019-09709-6

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