Structural Proton Diffusion along Lipid Bilayers

Abstract

For H(+) transport between protein pumps, lateral diffusion along membrane surfaces represents the most efficient pathway. Along lipid bilayers, we measured a diffusion coefficient of 5.8 x 10(-5) cm(2) s(-1). It is too large to be accounted for by vehicle diffusion, considering proton transport by acid carriers. Such a speed of migration is accomplished only by the Grotthuss mechanism involving the chemical exchange of hydrogen nuclei between hydrogen-bonded water molecules on the membrane surface, and the subsequent reorganization of the hydrogen-bonded network. Reconstitution of H(+)-binding sites on the membrane surface decreased the velocity of H(+) diffusion. In the absence of immobile buffers, structural (Grotthuss) diffusion occurred over a distance of 100 micro m as shown by microelectrode aided measurements of the spatial proton distribution in the immediate membrane vicinity and spatially resolved fluorescence measurements of interfacial pH. The efficiency of the anomalously fast lateral diffusion decreased gradually with an increase in mobile buffer concentration suggesting that structural diffusion is physiologically important for distances of approximately 10 nm.

Water at hydrophobic interfaces delays proton surface-to-bulk transfer and provides a pathway for lateral proton diffusion

“…According to such a calculation, D was more than an order of magnitude smaller than the diffusion coefficient of a proton carrier in bulk. In contrast, direct measurements on simple planar bilayers devoid of proton accepting proteinaceous residues revealed a D that was 10 times higher and proton residence times at the interface on the order of hundreds of milliseconds (8). Moreover, lateral diffusion along those bilayers persisted upon removal of titrable lipid groups.…”

“…To explain both the high surface diffusion coefficient and the long lateral diffusion span (5,8,22), the membrane-water interface must possess a feature that has thus far escaped notice. The simplest explanation would be that, in the absence of titrable groups (9), polar groups might stabilize the proton close to the interface.…”

110 Years of the Meyer–Overton Rule: Predicting Membrane Permeability of Gases and Other Small Compounds

“…Facilitated proton translocation by structural diffusion (Grotthuss mechanism) along these water wires implies that proton mass transfer does not occur, [14] since only the isolated protonic charge is moving along the hydrogen-bonded water network ( Figure 2). Although no detailed molecular picture is available yet explaining how the excess proton is shared among the water molecules [15,16] or how the required transient membrane defects are formed, [17] the unparalleled speed of Grotthuss diffusion is commonly accepted, as it also underlies lateral migration along membrane surfaces [18] and proton hopping through the membrane channels. [19][20][21] Since the exceptional rate of structural diffusion is limited to protons, the question arises as to whether other exceptions to the Meyer-Overton rule may exist and if yes, what the underlying mechanism may be.…”

Surface-coupled proton exchange of a membrane-bound proton acceptor

“…Enhancement of reaction rates between solute molecules and their target molecules on the surface and in the vicinity of biological membrane interfaces (e.g. ligand binding to membrane proteins) has been demonstrated in several studies and explained in terms of initial nonspecific binding of the solute molecules to the membrane followed by diffusion along the surface to their target molecules (1)(2)(3)(4)(5)(6)(7)(8). Studies on some specific membrane-bound proton pumps, for example cytochrome c oxidase or bacteriorhodopsin (9)(10)(11)(12), have revealed higher than diffusion-limited rates of proton uptake (9,(13)(14)(15).…”