Maxwells Demon Helps Run Your Muscles
James Clerk Maxwell once speculated that the second law of thermodynamics could be violated if an agent or “demon” could sort the hot and cold molecules at a barrier, thus overcoming the tendency toward thermal equilibrium. Something like this has been found at work in the molecular machines in our muscles. The actin-myosin motor is able to convert the random thermal motion (Brownian motion) of its environment into unidirectional motion due to the structural arrangement of its protein parts. The work was discussed in PNAS by researchers at Nagoya University in Japan.1
Myosin is like a robot walker on an actin racetrack. The robot uses ATP for energy. Each stepwise cycle requires ATP hydrolysis, but there is more energy in the action than can be accounted for by the ATP alone. The researchers determined that, as has long been suspected, the structure of the motor allows random thermal motion to be captured as with a ratchet. This “Brownian ratchet” mechanism helps propel the motor down the track in what they call a “functional funnel” of the energy landscape. “Our study embodies these theoretical models, indicating that a Brownian ratchet mechanism is likely to contribute substantially to the energy conversion of the actomyosin motor,” they said.
The researchers believe this clever mechanism underlies not only the actin-myosin complex but other molecular machines as well. Single-headed kinesin, for instance, moves in a similar way down its highway – the microtubule. Suddenly, it seems one can find Brownian ratchets everywhere in the cell:
Interestingly, it has been shown that this unidirectionality arises during the transition from the weak microtubule-binding to the strong microtubule-binding states; the same result has been reported for the conventional kinesin. These results imply that the energy landscape for the kinesin-microtubule interaction is asymmetric (with 8-nm periodicity of the microtubule), suggesting that the same Brownian ratchet mechanism as found here is inherent in the kinesin-microtubule system. Myosin V moves along the actin filament in a dimeric form with high processivity. A clock-escapement-like mechanism to regulate ADP release has been shown to play a critical role in the high processivity. In addition, the longer and more positively charged loop 2 of myosin V, which makes the energy landscape for the actin-myosin interaction deeper, would contribute to the high processivity. The asymmetric funnel would also help the detached head of myosin V, which exhibits an extensive Brownian motion, to quickly find the preferential binding site. A Brownian ratchet-like mechanism may also contribute to the force generation via a strain-dependent weak-to-strong transition, as has been shown by a recent in vitro SME [single-molecule experiments] of myosin VI.
From a general point of view, such an asymmetric funnel as found in the present study can be regarded as “functional funnel,” i.e., the energy landscape designed to fulfill functions efficiently and robustly. The functional funnel may be nature’s ingenious mechanism that enables molecular machines to harness the thermal noise, just as the “folding funnel” enables proteins to find their native structures efficiently and robustly via a Brownian search.
The “folding funnel” refers to the process by which proteins fold upon exiting the ribosome – another active area of research. It appears that thermal noise ratcheting also plays a role in achieving efficient and robust solutions quickly in that environment.
The authors did not speculate about how evolution might have hit upon this “ingenious mechanism” for efficient transportation. Instead, they said the mechanism was “designed to fulfill functions efficiently and robustly,” leaving the identity of the designer as a separate question. Their phrase “clock-escapement-like mechanism” recalls some familiar terminology from a long-forgotten, pre-Darwinian scholar by the name of William Paley.
1. Takano, Terada and Sasai, “Unidirectional Brownian motion observed in an in silico single molecule experiment of an actomyosin motor,” Proceedings of the National Academy of Sciences, published online April 12, 2010, doi: 10.1073/pnas.0911830107.
How Maxwell would have marvelled to know that the benevolent demons (actually, little robotic angels) he envisaged were busily at work inside him, keeping his heart beating, his lungs breathing, and his fingers writing across the page. His contemporary, Darwin, would undoubtedly have cringed to hear the phrase “clock-escapement-like mechanism” to describe something in the cells he dreamed were little more than undifferentiated blobs of jelly-like protoplasm.