TY - JOUR
T1 - Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling
AU - Dittmore, Andrew
AU - Silver, Jonathan
AU - Sarkar, Susanta K.
AU - Marmer, Barry
AU - Goldberg, Gregory I.
AU - Neuman, Keir C.
N1 - Funding Information:
We thank Hemai Parthasarathy and three anonymous referees for comments on the manuscript. This research was supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant R01AR040618, and National Cancer Institute Grant R01CA123363 (to G.G.).
PY - 2016/7/26
Y1 - 2016/7/26
N2 - 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 selfassembled biological filaments.
AB - 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 selfassembled biological filaments.
KW - Collagenase
KW - Matrix metalloproteinase
KW - Mechanosensing
KW - Pattern formation
KW - Single molecule
UR - http://www.scopus.com/inward/record.url?scp=84979610022&partnerID=8YFLogxK
U2 - 10.1073/pnas.1523228113
DO - 10.1073/pnas.1523228113
M3 - Article
C2 - 27402741
AN - SCOPUS:84979610022
SN - 0027-8424
VL - 113
SP - 8436
EP - 8441
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 30
ER -