Laboratory of Tissue Repair and Regeneration, Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, Canada.
Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, Canada.
Nat Commun. 2019 Apr 23;10(1):1850. doi: 10.1038/s41467-019-09709-6.
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.
巨噬细胞(Mϕ)-成纤维细胞相互作用协调损伤后的组织修复,而错误的交流可能导致病理性愈合和纤维化。我们表明,收缩的成纤维细胞在纤维胶原基质中产生变形场,为 Mϕ 提供深远的物理线索。在成纤维细胞或激活的微针产生的胶原变形场中,Mϕ 从数百微米远的地方向力源迁移。基质中动态力源的存在对于启动和指导 Mϕ 迁移至关重要。相比之下,成纤维细胞重塑活动或趋化信号导致的胶原凝聚和纤维排列既不是引导 Mϕ 迁移所必需的,也不是充分的。α2β1 整联蛋白和拉伸激活通道的结合介导 Mϕ 在纤维胶原 ECM 中的迁移和机械感知。我们提出,Mϕ 通过机械感知其基质中局部位移的速度,允许收缩的成纤维细胞在超过趋化梯度范围的距离上吸引 Mϕ。