In general, two different mechanisms control the flow of substances into and out of a cell. In one case, molecular pumps, driven by the cell's fuel ATP, actively force particular molecules and ions to flow in one direction, enabling the cell to maintain concentration differences across its membrane. In the other case, so-called passive channel proteins consume no energy but act as simple hatches into the cell, through which molecules can travel in either direction. Recently, this distinction has been called into question; passive channel proteins also act as directional transporters of material. However, thermodynamics requires that directional flow be driven by some energy source, but no such mechanism was well understood.

Recently former graduate student Ioan Kosztin, now an assistant professor at the University of Missouri-Columbia, and Professor Klaus Schulten showed that a specific asymmetrical channel protein from the bacterium Escherichia coli works like a ratchet to move glycerol against the normal flow, accelerating glycerol uptake by the cell when it is in short supply and reversing this process when there is too much of it. In a paper published in the December 3 issue of PRL and featured in Physical Review Focus, the researchers show that the key feature of the channel protein glycerol uptake facilitator (GlpF) is its assymetry, where the end of the protein protruding beyond the cell wall is structurally different from the end lying inside the cell (I. Kosztin and K. Schulten, "Fluctuation-Driven Molecular Transport Through an Asymmetric Membrane Channel," Phys. Rev. Lett. 93, 238102 [2004]).

As a glycerol molecule squeezes through the GlpF, it experiences a sequence of pushes and pulls, caused by vibrations of the cell membrane, allowing the GlpF to pass glycerol against a concentration gradient in a ratcheting motion. According to Kosztin and Schulten, the glycerol molecule acts a bit like a marble on a board covered with shingles that rocks back and forth. When the board is aligned so that the shingles lie atop one another as they do on a roof, the marble can roll freely from one tier to the next, but when the board tips the other way, the marble stops when it gets stuck on the raised edge of a shingle. Thus, as the board continues to rock, the marble travels in only one direction. In the first plausible demonstration of a rocking ratchet in a biological system, Kosztin and Schulten showed that the precise, assymmetrical shape of the GlpF potential should allow it to work this way for glycerol. The asymmetric glycerol potential leads to enhanced inward transport of glycerol in most cases, but for unfavorably high glycerol concentrations, outward transport is enhanced to protect a cell against poisoning.

But what energy source is coupled to the GlpF channel? Kosztin and Schulten suggest that a recent observation of twitching motions observed in cells might be the answer. Apparently, cells spend some metabolic energy to slightly contract and expand with a frequency in the kHz range. The reason for this twitching, observed by means of atomic force microscopy at the surface of cells, might be to assist passive membrane channels in directed transport.

If you would like to learn more about this exciting work, contact Professor Schulten.

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