Molecular electrometer and binding of cations to phospholipid bilayers

Abstract

Despite the vast amount of experimental and theoretical studies on the binding affinity of cations -especially the biologically relevant Na + and Ca 2+ -for phospholipid bilayers, there is no consensus in the literature. Here we show that by interpreting changes in the choline headgroup order parameters according to the 'molecular electrometer' concept [Seelig et al., Biochemistry, 1987, 26, 7535], one can directly compare the ion binding affinities between simulations and experiments. Our findings strongly support the view that in contrast to Ca 2+ and other multivalent ions, Na + and other monovalent ions (except Li + ) do not specifically bind to phosphatidylcholine lipid bilayers at sub-molar concentrations. However, the Na + binding affinity was overestimated by several molecular dynamics simulation models, resulting in artificially positively charged bilayers and exaggerated structural effects in the lipid headgroups. While qualitatively correct headgroup order parameter response was observed with Ca 2+ binding in all the tested models, no model had sufficient quantitative accuracy to interpret the Ca 2+ :lipid stoichiometry or the induced atomistic resolution structural changes. All scientific contributions to this open collaboration work were made publicly, using nmrlipids.blogspot.fi as the main communication platform.

Electrokinetic flow of an aqueous electrolyte in amorphous silica nanotubes

“…51 is −1.2k B T , relatively close to the value −0.9k B T following from our polarizable force field calculations ( Figure 4) and very different from the value of −4.0k B T suggested by the ion distributions (Figure 4) for the nonpolarizable force field system. Recent findings that electrometric measurements of Na + binding to phospholipid bilayers are overestimated by simulations using non-polarizable models 52 , and can be corrected by the inclusion of polarizability 53 , are also consistent with a conclusion that simulations using non-polarizable force fields lead to overestimates of the degree of Na + -silica binding. Certainly we can expect some sensitivity of our results to changes in the ion models; it has been noted by Bourg et al that the Joung-Cheatham ion parameters we have used can overestimate the entry of Na + ions into the hexagonal cavities of the surface of mica 54 , and perhaps changing to the models of Dang and Chang 55 would not so greatly overestimate the Na + binding.…”

“…Comparison with recent results showing that Na + binding to phospholipid bilayers is overestimated by non-polarizable force fields 52,53 , along with the large body of work showing that large anions should be modelled with polarizable force fields to properly describe their interfacial interactions 23,24 strongly suggests that some explicit treatment of polarizability should be included in future improvements in descriptions of the interaction with silica of both cations and anions, as well as with water.…”

The complex nature of calcium cation interactions with phospholipid bilayers

“…A novel force field with scaled charges was used to account in a mean-field fashion for polarization effects and thus reduce the known ion overbinding problem of standardly used empirical force fields3551. MD identified three calcium binding sites: carboxylate groups (POPS), phosphates, and carbonyl groups of sn-2 lipid chains.…”

Charge-dependent interactions of monomeric and filamentous actin with lipid bilayers

“…However, since divalent ions, like calcium, have a very high affinity to negatively charged membranes (33), the local ion concentration in the vicinity of the plasma membrane is much higher than the average cytosolic one, in line with our simulations and experiments. The effects of ions on the properties of lipid bilayers are, even in atomistic simulations, notoriously difficult to describe (34,87); however, the Martini model has been found to describe complex ion-induced processes like membrane fusion (60). Furthermore, as the interplay between the ions and actin is of central importance for this work, we explicitly compared the distribution of the Mg 2+ ions around G-actin of our CG model with an atomistic one (SI Appendix, Fig.…”