Membrane defect and water leakage caused by passive calcium permeation

Abstract

Our previous simulations found that permeation of Na+ and K+, in contrast with Cl−, causes significant membrane deformation and formation of a water wire in the membrane hydrophobic domain. Clearly, positive charges have a propensity to interact more strongly with lipids and thus induce serious defects to membrane. Since calcium is one of the most common and important metals in biology, we take it as template of a +2 charge and made the unprecedented effort to bring it across the membrane in molecular simulations. It is observed that under the ion/lipid ratio of 1:126 permeation of a +2 charge would badly disturb the bilayer structure, even lipid “flip-flop” is quite common, and cause leakage of water molecules by a widely-reported “All or None” manner, suggesting unassisted permeation of small molecules with 2 or more positive charges to be severe threats to cell membranes. More importantly, we found “All or None” leakage may be closely related to the “game” of hydrophilic and hydrophobic forces caused by positive charges. Our findings may be enlightening for the exploration of underlying mechanisms of the antimicrobial peptides and similar positively charged molecules acting on membranes.