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Biased diffusion of matrix metalloprotease degrading collagen fiber
Matrix metalloproteases (MMPs) are enzymes that degrade collagen fibers, which are the main component of the extracellular matrix and provide mechanical support for mammalian tissues. Collagen degradation is thus important for normal physiological functions including cell migration and wound healing however, the details of how MMPs interact with and degrade collagen fibers remain speculative. We measured the motion of single fluorescently labeled MMPs moving on collagen fibers with high spatial and temporal resolution. Our results suggest that cleavage of collagen by MMP1 results in both biased and hindered diffusive motion. Diffusion was neither biased nor hindered for an inactive MMP1 mutant or for MMP9, an enzyme incapable of cleaving collagen fibers. Conversely, hindered but unbiased diffusion of mutant MMP1 was observed following treatment of collagen fiber with active MMP1. These results support a burnt-bridge Brownian ratchet mechanism for MMP1 degrading collagen fiber. This model posits that enzyme cleavage introduces diffusion barriers that bias the motion of the cutting enzyme while hindering the motion of subsequent enzymes passing over the same site. Detailed analysis of the single-molecule trajectories further supports this model and allowed us to formulate a detailed kinetic scheme describing the interactions of MMP1 with collagen fiber.
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Contact : mathilde.reyssat@espci.fr