October 1, 2004 | David F. Coppedge

Burnt Bridges, Brownian Ratchets, and Self-Propelled Motors Keep Skin Young Looking

Rock climbers and cavers are familiar with mechanical devices called ascenders that enable them to climb ropes safely and easily.  Ascenders slide up the rope in one direction, but latch onto it tightly when pulled the other direction.  Now imagine the ascender by itself, hanging on the rope, in a flurry of winds blowing in all directions.  Despite the randomness of the gusts, the ascender might still make progress upward, because it slides up, but cannot slide down.  A team at Washington University School of Medicine, publishing in Science1 October 1, found something similar at work in the cell.  A molecular motor named collagenase MMP-1 uses the random thermal motion in its environment (Brownian motion) to self-propel itself along the triple tracks of collagen molecules.
    “Molecular motors,” like the motors in our experience, are machines that convert energy into motion, but in the cell, they’re constructed of protein.  Many kinds are known: propellers, railroad cars, walkers and other exotic things, but most of them extract chemical energy from the “energy currency” of the cell, ATP.  Collagenase uses the free thermal motion of the environment to its advantage.  Acting as a “Brownian ratchet,” it converts random fluctuations into unidirectional motion.  This is the first molecular motor found to work outside the cell.
    Collagen is one of the most plentiful proteins.  It’s an important structural component of many tissues, not the least of which is skin.  Composed of three strands of rope-like polymers, it provides both strength and flexibility to skin and other tissues.  (For background on collagen and collagenase, see this description on a Wayne State biology site.)  Sometimes collagen fibrils need to be disassembled, however, and that’s the job of collagenase.  Providentially, collagen comes with joints called “cleavage sites” where the strands can be easily broken by the enzymes for quick recycling.  The collagenase motor clings like an ascender to a rope and walks up the collagen fiber to the nearest cleavage site.  Self-propelled by Brownian motion, it goes into action splitting the fibrils as needed.  What keeps it from falling back down?  Without a ratchet or clutch mechanism, all the motor could hope for when subjected to random forces is symmetric back and forth motion on the cable.  Collagenase, it turns out, uses a strategy called the “burnt bridge” technique.
    If you were on a monorail buffeted by random winds, but needed to get somewhere, you could avoid rolling backward, away from your destination, by burning your bridges behind you.  Assuming your technique braked any backward motion (rather than making you fall off), this strategy would result in a net forward “propulsion.”  The collagenase motor does this by “digesting” the fiber after it passes by, preventing backward motion, and allowing the next gust of thermal energy to propel it forward.  Wouldn’t this result in traffic jams, when multiple motors bunch up against cleavage sites?  No; the motors can switch to nearby collagen fibers.  “Relief of the traffic jam is achieved by the transfer of the trapped enzyme to new tracks,” the authors explain.
    The research team found that this form of propulsion is about 15% efficient but costs no ATP.  As a result, collagenase works its way along the fiber at about 4.5 micrometers per second.  On a molecular scale, that’s scootin’.  On our scale, that would translate to about a thousand miles an hour.  Imagine moving that fast on a highway with no gasoline, extracting energy from the road!  Senior author Dr. Gregory Goldberg expressed some wonder at this mechanism used by collagenase: “with our model, a whole new principle emerges in which molecular motors in the extracellular matrix operate by extracting energy from the very track they move upon.”
    What does this mean to you and me?  “By digesting collagen, enzymes such as MMP-1 initiate tissue remodeling, which can have a variety of purposes from organ development to tissue repair to metastatic invasion of tumors.”  A summary on EurekAlert explains,

The researchers propose the molecular motor contributes to restructuring the extracellular support matrix during tissue growth and development or wound repair or even during cancerous invasion of tissues.  Because MMP-1 moves directionally, it can serve as a clutch, assisting cell locomotion along networks of collagen in tissues.  Further, motion along the precisely aligned collagen filaments directs the proper development of individual tissue types.

Your skin cells continually export these molecular machines into the extracellular matrix to break down collagen for repairs, so that your scars can heal and you can grow fresh skin.  They might be involved in many other things, like moving the entire cell along on “a ‘no-skid’ surface generated by the digestion of collagen fibrils,” the authors propose (is this what makes our skin crawl?)  If uncontrolled, though, the scissors action of these molecular machines would wreak havoc on our skin, making us melt like the wicked witch of the west.  Not to worry; everything is tightly regulated.  Goldberg reassures us, “The enzymes aren’t loose and disorganized where they would just end up destroying the matrix.  By mechanisms that we are exploring further, they create a relation between cells and the structures in the matrix.  It’s a very elegant system.”  For soft, fresh, beautiful skin, ratchet up and burn your bridges behind you.

1Saffarian, Goldberg et al., “Interstitial Collagenase Is a Brownian Ratchet Driven by Proteolysis of Collagen,” Science, Vol 306, Issue 5693, 108-111, 1 October 2004, [DOI: 10.1126/science.1099179].

Can’t get enough of these molecular machines.  Wow.  Giveaway question: how many times was evolution mentioned in this paper?  What is an integer less than one?

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