title: Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling.
abstract: Fibrillar collagen, an essential structural component of the extracellular matrix, is remarkably resistant to proteolysis, requiring specialized matrix metalloproteinases (MMPs) to initiate its remodeling. In the context of native fibrils, remodeling is poorly understood; MMPs have limited access to cleavage sites and are inhibited by tension on the fibril. Here, single-molecule recordings of fluorescently labeled MMPs reveal cleavage-vulnerable binding regions arrayed periodically at ∼1-µm intervals along collagen fibrils. Binding regions remain periodic even as they migrate on the fibril, indicating a collective process of thermally activated and self-healing defect formation. An internal strain relief model involving reversible structural rearrangements quantitatively reproduces the observed spatial patterning and fluctuations of defects and provides a mechanism for tension-dependent stabilization of fibrillar collagen. This work identifies internal-strain-driven defects that may have general and widespread regulatory functions in self-assembled biological filaments.
authors.affiliation: Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Andrew
authors.initials: A
authors.lastname: Dittmore
authors.affiliation: Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Silver
authors.affiliation: Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892;
authors.forename: Susanta K
authors.initials: SK
authors.lastname: Sarkar
authors.affiliation: Division of Dermatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63130.
authors.forename: Barry
authors.initials: B
authors.lastname: Marmer
authors.affiliation: Division of Dermatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63130 neumankc@mail.nih.gov goldberg@medicine.wustl.edu.
authors.forename: Gregory I
authors.initials: GI
authors.lastname: Goldberg
authors.affiliation: Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892; neumankc@mail.nih.gov goldberg@medicine.wustl.edu.
authors.forename: Keir C
authors.initials: KC
authors.lastname: Neuman
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism*; D024022:Fibrillar Collagens / Q000737:chemistry / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000378:metabolism*; D055595:Mechanical Phenomena; D011485:Protein Binding; D059748:Proteolysis; D051381:Rats; D000072760:Single Molecule Imaging / Q000379:methods; D013623:Tail; D013710:Tendons / Q000378:metabolism*
chemical_list: D024022:Fibrillar Collagens; D020782:Matrix Metalloproteinases
keywords: collagenase; matrix metalloproteinase; mechanosensing; pattern formation; single molecule