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Mechanical load induces a 100-fold increase in the rate of collagen proteolysis by MMP-1.


ABSTRACT: 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.

SUBMITTER: Adhikari AS 

PROVIDER: S-EPMC3320677 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Mechanical load induces a 100-fold increase in the rate of collagen proteolysis by MMP-1.

Adhikari Arjun S AS   Chai Jack J   Dunn Alexander R AR  

Journal of the American Chemical Society 20110119 6


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 w  ...[more]

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