A Little Tug Speeds Up Collagen Cleavage

Mechanical stress increases the rate at which structural collagen is degraded by the enzyme matrix metalloproteinase-1 (MMP-1), according to a study by Stanford University chemical engineers (J. Am. Chem. Soc., DOI: 10.1021/ja109972p). Mechanical stress is known to affect the composition and structure of the collagen-containing extracellular matrix (ECM) in embryonic development and some diseases. But how this force exerts its influence is poorly understood. Alexander R. Dunn, Arjun S. Adhikari, and Jack Chai used a magnetic bead assay to measure the effect of force on the rate at which MMP-1 snips collagen. The researchers attached one end of each collagen trimer to a surface and the other end to a magnetic bead. Bead detachment from the surface signaled that MMP-1 had cleaved the collagen. They found that a mechanical load of 13 pico­new­tons increased the rate of collagen cleavage 81-fold. The team proposes a model in which the mechanical force stretches and unwinds the collagen, allowing MMP-1 to rapidly cleave the collagen triple helix. The findings suggest “a possible role for mechanical force in the regulation of ECM remodeling,” the researchers write.