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 24.10.2007   Карта сайта     Language По-русски По-английски
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24.10.2007


Instant insight: Walking in a hurricane



23 October 2007



Dean Astumian from the University of Maine, Orono, US, uncovers the mysteries of Brownian molecular machines


When we think of a motor that can drive movement at velocities of several hundred times its own length per second, we probably picture a massive oily machine such as the four stroke internal combustion engine. But biomolecular motors - proteins such as kinesin that move and assemble biological structures - are a just few nanometres in size and can move at nearly a micrometre per second along a polymeric track. These motors are often described by biologists in terms of automobiles or even steam engines. They are said to be driven by a 'power stroke' - a conformational change triggered by, for example, adenosine triphosphate (ATP) hydrolysis.


 


Molecular motor








The paths of a Brownian motor are determined by the stabilities of its possible states, and by the heights of the barriers between these



 


However, there is a problem with these easily understandable large scale descriptions of molecular motors. The mechanical principles called to mind by association with familiar machines simply do not apply to nanoscale systems such as molecular motors.


For molecules in water, viscosity dominates inertia - in order to move forward, a molecular motor must 'swim in molasses'. Further, the thermal noise power exchanged reversibly between the motor and its environment due to random collisions with water molecules is much larger than the power provided by the 'power stroke'. One might think that moving in a specific direction would be as difficult as walking in a hurricane. Yet biomolecular motors move and accomplish their function with almost deterministic precision.



"Biomolecular motors move and accomplish their function with almost deterministic precision"

The emerging picture of how biomolecular motors operate is known as a Brownian motor mechanism. The motor is viewed as a molecule in mechanical equilibrium undergoing a random walk on a lattice of states that are distinguished from each other by their spatial position and their chemical substituents. The different stabilities of the states and the barriers between them restrict the path that the molecule can follow across the lattice. The chemical free energy of the fuel sets the direction along the preferred path.


Take as an example, a single kinesin molecule at chemical equilibrium. The molecule vigorously moves about on its polymeric track because of thermal noise, sometimes stepping left, sometimes stepping right, sometimes binding ATP, sometimes binding ADP (adenosine diphosphate), sometimes hydrolyzing ATP, sometimes making ATP from ADP. The chemical equilibrium is maintained not by a static opposition of equal magnitude forces, but by dynamic processes in which every forward motion is exactly as likely as the microscopic reverse of that motion. When the chemical potential of ATP is higher than that of ADP in the bulk solution, ATP hydrolysis then drives directed motion by mass action.


When comparing this picture of a biomolecular motor with that of a very small macroscopic motor, we see a stark contrast. In his now famous after dinner talk, 'Plenty of Room at the Bottom', Richard Feynman issued a challenge to build a motor that, not counting the power supply and connecting wires, would fit into a cube 1/64th of an inch (a bit less than half a millimetre) on a side. This challenge was successfully accomplished by an engineer, William McClellan, only a year later. It is reported that Feynman was disappointed that no new principles were applied; McClellan's motor was simply a tour de force of miniaturization. When viewed (under a microscope!) without any source of external energy the motor does absolutely nothing - it simply sits there, totally still.



"A uniquely chemical approach to controlling motion at the nanoscale"

A key difference between Brownian and mechanical motors is that, due to thermal noise, a nanoscale system explores all possible motions and configurations. This feature allows a uniquely chemical approach to controlling motion at the nanoscale. By using chemical design and input energy to prevent motion that we do not want, what is left behind is the motion that we do want.


Insight into the importance of Brownian motion for molecular motors paves the way toward rational design of molecular machines for a wide range of tasks at the nanometre scale.


Dean Astumian



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