Muscling in on molecular machines
The concept of a “power stroke” – a free-energy releasing shape change of a protein – appears in almost every textbook that deals with the molecular details of muscle, bacterial flagella, and many other bio-molecular machines. Researchers have now shown that the power stroke model is wrong as an explanation of how chemical energy is used by a molecular machine to do mechanical work. Instead the directionality is controlled entirely by the gating of the chemical reaction that provides the fuel for the machine. Achieving directed motion of a molecular machine is much more a problem of molecular recognition than it is of nano-mechanics, as illustrated in Fig. 1 for a schematic molecular machine driven by ATP hydrolysis, the common energy currency in cells.
The better understanding of bio-molecular motors provided by the recent research has led to progress in the design of synthetic molecular machines. One specific example involves threading several rings onto a long rod by a “molecular pump” shown in Fig. 2. A key step in the function of this synthetic pump is the oxidation of a recognition site on the rod. In the reduced state (purple) there is an attractive interaction between the ring and the recognition site, but on oxidation (blue) the interaction becomes repulsive. The movement of the ring from the oxidized recognition site to a collecting chain is very reasonably termed a power stroke.
By repetitively changing the redox potential (and hence the reduction/oxidation of the recognition site) several rings can be pumped onto the collecting chain to form a non-equilibrium complex, a structure that would exist in only negligible amounts in the absence of energy input that is provided by repetitively changing the redox potential. The power stroke for this pump is absolutely essential.
On further consideration, however, it soon became apparent that a power stroke is not sufficient to allow the energy released by chemical catalysis to drive pumping. Even more surprisingly perhaps, the power stroke is not even necessary. The essential requirement is seen to be a mechanism for gating the catalysis such that reaction with substrate is fast and reaction with product slow in one state of the mechanical cycle, and reaction with substrate slow and reaction with product fast in a different state of the mechanical cycle, thus assuring that the mechanical and chemical steps are interleaved with one another, a condition that, combined with energy from the catalyzed reaction, is both necessary and sufficient for pumping of the rings onto the collecting chain. This mechanism has been termed an information ratchet because the essential feature is that the specificity of the catalytic active site is controlled by information about the mechanical state of the motor molecule.
Ongoing efforts devoted to the design and construction of synthetic molecular pumps and motors will result both in better understanding of bio-molecular machines, and in the development of tools for harnessing the power of molecule by molecule assembly.
R. Dean Astumian
Dept. of Physics, Univ. of Maine
Huxley’s Model for Muscle Contraction Revisited: The Importance of Microscopic Reversibility.
Top Curr Chem. 2015
Design and Synthesis of Nonequilibrium Systems.
Cheng C, McGonigal PR, Stoddart JF, Astumian RD
ACS Nano. 2015 Sep 22