Mechanism of Unassisted Ion Transport across Membranes

Michael A. Wilson and Andrew Pohorille

In contemporary cells ions play an essential role in a wide variety of processes, such as bioenergetics, signaling and catalysis of chemical reactions. They are also needed for maintaining the biologically active structures of biopolymers. Considering the widespread importance of ions in present-day cellular biology, they must have been importantly involved in the emergence of life.

To enter cells ions must permeate lipid membranes which form cell walls. This process requires large activation energy associated with transferring ions from the polar aqueous environment to the nonpolar interior of the membrane. To lower the activation energy in contemporary cells, ion transport is aided by ion channels, carriers and pumps located in membranes. However, at the earliest stage of cellular evolution ion transport must have proceeded without assistance of these highly evolved molecules.

Unassisted membrane permeability to ions can be readily estimated from a standard model in which the ion is transferred through the membrane represented as a structure of fixed width, poorly penetrable by water. These estimates lead to the conclusion that membranes are practically impermeable to ions. These results are in conflict with expermental measurements which yield permeability of model membranes to ions 13-15 orders of magnitude higher. This discrepancy indicates that the standard model ignores some essential features of the transfer process that considerably lower ionic premeabilities.

To identify these features we performed large--scale commputer simulations of unassisted transport across the membrane of two biologically essential ions - Na⁺ and Cl^-. We found that as the ions moved into the membrane interior, it created a local deformation, whereby water molecules and polar head groups of membrane--forming lipids, normally restricted to the surface of the membrane, ``followed'' the ions into the nonpolar interior (see Figure ). As the ions crossed the midplane of the membrane the deformation ``switched sides''; the initial defect slowly relaxed and, instead, a defect was formed in the outgoing side of the membrane. During the whole process of transfer the ions remained well solvated by both, water and polar lipid head groups. Membrane defects and ion solvation considerably lower the activation energy to unassisted ion transport rendering this process feasible.

The results of this study also offer valuable insight into a broad range of other chemical and biochemical processes, such as assisted ion transport, charge stabilization inside membranes, time--controlled drug delivery and ion transport between two immiscible liquids, fundamental in electrochemistry.