BIOPHYSICAL THEORY AND MODELING |
Ion leakage through transient water pores in protein-free
lipid membranes driven by transmembrane ionic charge imbalance
Andrey A Gurtovenko 1 and Ilpo Vattulainen 2*
1 University of Bradford, UK
2 Tampere University of Technology, Finland
* To whom correspondence should be addressed. E-mail: ilpo.vattulainen{at}csc.fi.
Submitted on August 4, 2006
Revised on September 25, 2006
Accepted on 4 December 2006
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Abstract |
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We have employed atomic-scale molecular dynamics simulations to address ion leakage through transient water pores in protein-free phospholipid membranes. Our results for phospholipid membranes in aqueous solution with NaCl and KCl salts show that the formation of transient water pores and the consequent ion leakage can be induced and be driven by a transmembrane ionic charge imbalance, an inherent feature in living cells. These processes take place if the gradient is large enough to develop a sufficiently significant potential difference across the membrane. The transport of cations and anions through the water pores is then witnessed; it discharges the transmembrane potential, considerably reduces the size of a water pore, and makes the water pore metastable, leading eventually to its sealing. The ion transport is found to be sensitive to the type of ions. It turns out that Na+ and Cl ions leak through a membrane at approximately the same ratio in spite of the fact that Na+ ions are expected to experience lower potential barrier for the permeation through the pore. This is due to strong interactions of sodium ions with the carbonyl region of a phospholipid membrane as well as with lipid headgroups forming pore "walls", considerably slowing down the permeation of sodium ions. In contrast, we observed a pronounced selectivity of a phospholipid membrane to the permeation of potassium ions as compared to chloride ions: Potassium ions, being larger than sodium ions, interact
only weakly with phospholipid headgroups, so that these interactions are not able to compensate a large difference in free-energy barriers for permeation of K+ and Cl- ions. These findings are found to be robust to a choice of force-field parameters for ions (tested by Gromacs and Charmm force-fields for ions). What is more, a potassium ion is found to be able to permeate a membrane along an alternate, "water-defect-mediated" pathway without actual formation of a pore. The "water-defect-mediated" leakage involves formation of a single water defect only and is found to be at least one order of magnitude faster than the pore-mediated ion leakage.
Key Words:
Computer simulations, Ion leakage, Lipid membrane, Molecular dynamics, Water pore
