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Science 1 October 2004:
Vol. 306. no. 5693, pp. 108 - 111
DOI: 10.1126/science.1099179
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Reports

Interstitial Collagenase Is a Brownian Ratchet Driven by Proteolysis of Collagen

Saveez Saffarian,1 Ivan E. Collier,2 Barry L. Marmer,2 Elliot L. Elson,1 Gregory Goldberg1,2*

We show that activated collagenase (MMP-1) moves processively on the collagen fibril. The mechanism of movement is a biased diffusion with the bias component dependent on the proteolysis of its substrate, not adenosine triphosphate (ATP) hydrolysis. Inactivation of the enzyme by a single amino acid residue substitution in the active center eliminates the bias without noticeable effect on rate of diffusion. Monte Carlo simulations using a model similar to a "burnt bridge" Brownian ratchet accurately describe our experimental results and previous observations on kinetics of collagen digestion. The biological implications of MMP-1 acting as a molecular ratchet tethered to the cell surface suggest new mechanisms for its role in tissue remodeling and cell-matrix interaction.

1 Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
2 Division of Dermatology, Washington University School of Medicine, St. Louis, MO 63110, USA.

* To whom correspondence should be addressed. E-mail: goldberg{at}medicine.wustl.edu

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