Mechanical load induces a 100-fold increase in the rate of collagen proteolysis by MMP-1.
Although mechanical stress is known to profoundly influence the composition and structure of the extracellular matrix (ECM), the mechanisms by which this regulation occurs remain poorly understood. We used a single-molecule magnetic tweezers assay to study the effect of force on collagen proteolysis by matrix metalloproteinase-1 (MMP-1). Here we show that the application of ∼10 pN in extensional force causes an ∼100-fold increase in proteolysis rates. Our results support a mechanistic model in which the collagen triple helix unwinds prior to proteolysis. The data and resulting model predict that biologically relevant forces may increase localized ECM proteolysis, suggesting a possible role for mechanical force in the regulation of ECM remodeling.
Department of Chemical Engineering, Stanford University, Stanford, California 94305, United States.
Arjun S
AS
Adhikari
Jack
J
Chai
Alexander R
AR
Dunn
D000595:Amino Acid Sequence; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D055595:Mechanical Phenomena; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D059748:Proteolysis
D010446:Peptide Fragments; D003094:Collagen; D020781:Matrix Metalloproteinase 1
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