Powering the Brownian ratchet: a model of an extracellular motor driven by proteolysis of collagen

Saveez Saffarian
Kirchhausen Lab


We recently discovered 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. Here we developed a theoretical model within a framework consistent with the experimental measurements on MMP-1 at zero load. We considered an effect of varying degree of coupling of free energy from collagen proteolysis and subsequent fibril unfolding on the MMP-1 motion. The model predicts that under certain conditions this new chemo-mechanical mechanism can power the MMP-1 Brownian ratchet to create a molecular motor with a sufficient stall force to be of biological significance. Surprisingly, in this model the stall force varies nonlinearly with the coupling fraction. In addition, application of the increasing external force initially causes an increase in the velocity of the motor up to a maximum before it begins to stall. A relatively low stall force is predicted for individual MMP-1 motor molecules. Loading a two MMP-1 molecule cluster is capable of creating a force in the range of 5pN, an order of magnitude increase compared to the single MMP-1 molecule.


S Saffarian, I E Collier, B L Marmer, E L Elson & G Goldberg, "Interstitial collagenase is a Brownian ratchet driven by proteolysis of collagen", Science 306:108-11, 2004. PubMed