The Physics of the Kidney,"
The Physics of the Kidney
The kidneys filter a bathtub of water a day without letting protons pass, posing a puzzle to biological physicists. Led by Swanlund Professor of Physics Klaus Schulten, a group of scientists at the University of Illinois solved this puzzle, documenting a "ballet," in which "dancers" cross a stage in a billionth of a second. The stage is a class of proteins found in kidneys, but also in all other organs, in plants, and in bacteria; the dancers are water molecules. The performance, captured by supercomputer simulation and crystallography, reveals new insights for biomedical researchers on the controlled movement of water through cell walls (see Emad Tajkhorshid, Peter Nollert, Morten Ø. Jensen, Larry J. W. Miercke, Joseph O'Connell, Robert M. Stroud, and Klaus Schulten, "Control of the selectivity of the aquaporin water channel family by global orientational tuning," Science 296, 525-530 (2002)).
Aquaporins are membrane water channels that play critical roles in controlling the water contents of cells. These channels are widely distributed in all kingdoms of life, including bacteria, plants, and mammals. More than ten different aquaporins have been found in the human body, and several diseases, such as congenital cataracts and nephrogenic diabetes insipidus, are associated with the impaired function of these channels.
Aquaporins form tetramers in the cell membrane and facilitate the transport of water and, in some cases, other small solutes across the membrane. They are, however, completely impermeable to charged species, such as protons—a remarkable property that is critical for the conservation of a membrane's electrochemical potential, but paradoxical at the same time, since protons can usually be transported readily through water molecules.
In one of the most advanced biomolecular simulations ever done, employing the largest supercomputers available to civilian scientists in the United States, Schulten's group simulated the channel, membrane, and water molecules on both sides, comprising a system of more than 100,000 atoms. The simulations revealed that the water molecules pass single-file through the channel. Upon entering, the oxygen atom of the water molecule faces down the channel. Midstream, the molecule reverses orientation, with the oxygen atom facing up. While passing through the channel, the ballet of water molecules streams through, always entering face down and leaving face up.
"The strictly opposite orientations of the water molecules keep them from conducting protons, while still permitting a fast flux," Schulten said. "If these channels were leaky for ions, the electrical potentials of the cell walls would be abolished, leading to a complete breakdown of cell metabolism." The flip at the center of the channel (see the animation), breaks the alternative donor-acceptor arrangement that is necessary for proton translocation.
More information on this exciting work is available here. Support was provided by the National Institutes of Health. The computations were carried out at the Pittsburgh Supercomputer Center.