Physics Colloquium, October 23, 2007
Can the Collagenase Brownian Ratchet Exert a Significant Force on a Cell? Elliot L. Elson

Washington University School of Medicine, St. Louis, Missouri

Collagen, an abundant protein in all animals, forms triple helical "monomers" about 300 nm long that are commonly organized into fibrils. A fibril is a bundle of long parallel filaments each composed of many monomers set end to end. MMP-1 is a collagenase, an enzyme that digests collagen fibrils. Fluorescence microscopy and correlation spectroscopy have demonstrated that MMP-1, undergoes biased motion along collagen fibrils coupled to proteolysis of the fibrils. The molecule functions as an ATP-independent Brownian ratchet according to a "burnt bridges" mechanism (Mai, 2001; Saffarian, 2004). The molecule diffuses randomly on a collagen track until it reaches a cleavage site. Upon cleavage of the collagen track the enzyme molecule remains on the "downstream" side of the break and cannot diffuse "upstream" across the break. It then diffuses randomly until reaching the next cleavage site 300 nm downstream and the process is repeated. Is this biased motion merely an accidental consequence of the mechanism of enzymatic digestion of collagen or does it have a biological role? The mechanism predicts that the energy providing the driving force for motion is k_BT, and so the force would be small. Nevertheless, considerable energy is released upon cleavage of the track that might provide a greater driving force (Saffarian, 2006). How might this force be used?

References:
Mai, J., I. M. Sokolov and A. Blumen (2001). "Directed particle diffusion under "burnt bridges" conditions." Physical Review E: Stat, Nonlin, Soft Matter Physics 64(1-1): 011102/1-011102/4.

Saffarian, S., I. E. Collier, B. L. Marmer, E. L. Elson and G. Goldberg (2004). "Interstitial collagenase is a Brownian ratchet driven by proteolysis of collagen." Science 306(5693): 108-11.

Saffarian, S., H. Qian, I. Collier, E. Elson and G. Goldberg (2006). "Powering a burnt bridges Brownian ratchet: A model for an extracellular motor driven by proteolysis of collagen." Phys Rev E Stat Nonlin Soft Matter Phys 73(4 Pt 1): 041909/1-041909/4.

Authors:
Elliot L. Elson² , Ivan E. Collier¹, Saveez Saffarian³, Barry L. Marmer¹, and Gregory Goldberg^1,2.

From the Division of Dermatology¹, Department of Biochemistry and Molecular Biophysics², Washington University School of Medicine, St. Louis, Missouri 63110; and Cell Biology Department³, Harvard Medical School/CBR, 200 Longwood Ave., Boston, Ma 02115.

Dr. Elson's Web Site

Dr. Elson's e-mail: elson@wustl.edu

4:00 p.m., Physics Research Building (PRB), Room 1080

Reception at 3:45 p.m., Atrium, PRB