Single file water transport through nanopores

Confinement of water by pore geometry to a one-dimensional file of molecules alters its physico-chemical properties. These changes are believed to be responsible for the discrepancies in water mobilities (i) predicted from continuum or kinetic models, (ii) determined by molecular dynamics simulations and (iii) derived from the experiment. Accordingly, (i) friction is thought to linearly reduce mobility with channel length or (ii) salvation is believed to form the main energetic barrier so that mobility is independent on channel length or (iii) multiple water binding sites in the pore are postulated to explain the observed exponential decrease of mobility with pore length. Goal of the current proposal is to reveal the true molecular mechanism of single file transport. It addresses the following questions: (i) What determines the energetics of water entry into the pore? Do lipid charged headgroups or amino acids at the channel mouth have a significant effect on water dehydration? Does the presence of polar lipid headgroups or carbonyl groups play a role? (ii) What determines the height of the internal barriers? Is it possible to tune these barriers by introducing hydrophobic elements into the pore wall? (iii) How important is the strength of the hydrogen bonding between the permeating water molecules, i.e. is there an isotope effect in single file water transport? To answer these questions osmotic water transport through reconstituted nanopores is measured by electrochemical microscopy. To derive the single nanopore permeability, the number of pores is counted by current measurements under voltage clamp conditions. The results are expected to contribute to the understanding of hydrophobic gating of receptors, single file transport through ion channels, and the development of nanofluidics devices.

Life on earth is unthinkable without water. Every organism, every tissue and every cell has established an elaborate system to control the amount of water passing through its borders, to maintain the necessary balance of water uptake and release. We are interested in finding out how water transport across the borders of the smallest unit of living organisms, the cell membrane, happens. More precisely, we pose the question as to how water molecules squeeze through extremely narrow channels in those membranes. These channels have a lumen that is no wider than the diameter of one water molecule. Such channels are very important in our everyday life: they do not only selectively transport water, some of them also transport ions. In fact, all of our sensory organs as well as the transmission of the information from our eyes, nose, or ears to our brain and then further from the brain to our legs and hands relies on these kinds of channels. Intuitively, one tends to compare the passage of water molecules and ions with the passage of hard spheres through macroscopically large pipes. However, the macroscopic laws of hydrodynamics do not apply. First of all, there is no parabolic streaming profile within the narrow channels, since they are only one molecule wide. There is also perfect slip at the channel walls: if the no-slip condition would apply for the first layer of water molecules, there would be no water flux through such narrow channels. Currently, it is totally unclear what may substitute for the macroscopic laws of hydrodynamics, i.e. a physical description of the microscopic laws of hydrodynamics is not available. The project aims to distinguish between two scenarios: 1. The entrance of water molecules into the channel is the rate limiting step; 2. Interactions of water molecules with the channel wall govern the water flux. Upon entering the channel water loses two of its four water neighbors. This is an energetically unfavorable state because of the reduced number of hydrogen bonds. We have now shown that the barrier at the entrance may be reduced by placing positive charges at the channel mouth. Water is less tightly bound to those charges than to negative ones. In consequence, the narrow pores are able to channel about seven times more water than in the absence of the positive charge. Residues in the channel wall that donate or receive hydrogen bonds may have an opposite, but equally large effect: the unitary water permeability decreases exponentially with the number of those residues. Thus, we conclude that neither of the two scenarios is correct. Both the residues at the channel mouth and the residues forming the channel wall make equally sized contributions to the unitary water permeability of narrow channels.