Nanomedicine, Volume I: Basic Capabilities
© 1999 Robert A. Freitas Jr. All Rights Reserved.
Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999
3.4.1 Transporter Pumps
While gated channels enable ions to flow rapidly through membranes in a thermodynamically downhill direction, active pumps use a source of free energy to force an uphill transport of ions or molecules. In biology the energy supply is usually ATP or photons of light; medical nanomachines can make use of vastly more diverse energy sources (Chapter 6). Actually, the term "pump" may be something of a misnomer because the action is highly specific -- only one or a very small number of molecular species are selectively transported.
Molecular pumps generally operate in a four-phase sequence: (1) recognition (and binding) by the transporter of the target molecule from a variety of molecules presented to the pump in the input substrate; (2) translocation of the target molecule through the membrane, inside the transporter mechanism; (3) release of the molecule by the transporter mechanism; and (4) return of the transporter to its original condition, so that it is ready to accept another target molecule. Such molecular transporters that rely on protein conformational changes are ubiquitous in biological systems, and are illustrated schematically in Figure 3.5.
The minimum energy required to pump molecules is the change in free energy DG in transporting the species from one environment having concentration c1 to a second environment having concentration c2, given by:
where k = 0.01381 zJ/K (Boltzmann constant), T = 310 K, Ze is the number of charges per molecule transported (i.e., the valency), F = 9.65 x 104 coul/mole (Faraday constant), DV is the potential in volts across the membrane, and NA is Avogadro's number. So for example, transport of an uncharged molecule across a c2/c1 = 103 gradient (typical in biology) costs ~30 zJ. An extremely aggressive c2/c1 = 106 concentration gradient costs ~60 zJ/molecule, plus another ~30 zJ/ion if we are moving Ca++ ions against a 100 mV potential. An artificial nanopump of dimension ~10 nm moving at a conservative ~1 cm/sec velocity operates at MHz frequencies, transporting ~106 molecules/sec for a continuous power consumption of ~0.03 pW at c2/c1 = 103. Such a pump has a mass ~10-21 kg.
Transporter pumps need not be limited to the movement of a single molecular species in a single direction, which biochemists call a uniport transport mechanism.3649 Numerous well-known biological systems are capable of moving two molecules simultaneously in one direction (symport mechanisms), two molecules sequentially in opposite directions (antiport mechanisms),3642-3648 and charged molecules in one direction only, thus building up an electrical charge on one side of the membrane (electrogenic mechanisms).3633-3637,3643 Such pumps exist in nature for numerous ions, amino acids, sugars, and other small biomolecules.398 Active drug efflux systems400 and multidrug resistance399 are made possible by the expression of bacterial genes coding for molecular pumps that are constantly evolving new specificities to increasing numbers of microbicidal drugs.
The action of the Na+ - K+ antiporter, a familiar ion pump present in all mammalian cells, is illustrated in Figure 3.6. Three Na+ and two K+ ions are transported per 10 millisec cycle, requiring the hydrolysis of one ATP molecule to ADP to drive the conformational changes. (More than one-third of the ATP consumed by a resting animal is used to pump these two ions.) Hydrolysis of ATP liberates ~80 zJ/molecule of free energy, so the antiporter is transporting Na+ and K+ at a cost of 16 zJ/ion at a 0.5 KHz frequency. Pump site density is ~1000/micron2 of cell membrane in neural C fibers.800 (The Na+ - K+ pump can also be operated in reverse to synthesize ATP from ADP by exposing the mechanism to steep ionic gradients.) By contrast, artificial nanomechanical antiporter and symporter devices will operate at MHz frequencies.1177 They should be able to transport much larger molecules, and may also be fully reversible.
Last updated on 7 February 2003