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Transmembrane Potential of Physiologically Relevant Model Membranes: Effects of Membrane Asymmetry

submitted on 14.06.2020, 00:47 and posted on 16.06.2020, 09:48 by Xubo Lin, Alemayehu A. Gorfe
Transmembrane potential difference (𝑉௠) plays important roles in regulating various biological
processes. At the macro level, 𝑉௠ can be experimentally measured or calculated using the Nernst
or Goldman-Hodgkin-Katz equation. However, the atomic details responsible for its generation
and impact on protein and lipid dynamics still need to be further elucidated. In this work, we
performed a series of all-atom molecular dynamics simulations of symmetric model membranes of
various lipid compositions and cation contents to evaluate the relationship between membrane
asymmetry and 𝑉௠. Specifically, we studied the impact of the asymmetric distribution of POPS (1-
palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine), PIP2 (phosphatidylinositol 4,5-bisphosphate),
𝑁𝑎ା, 𝐾ା and 𝐶𝑎ଶା on 𝑉௠ using atomically detailed molecular dynamics simulations of symmetric
model membranes. The results suggest that, for an asymmetric POPC-POPC/POPS bilayer in the
presence of NaCl, enrichment of the monovalent anionic lipid POPS in the inner leaflet polarizes
the membrane (∆𝑉௠ < 0). Intriguingly, replacing a third of the POPS lipids by the polyvalent
anionic signaling lipid PIP2 counteracts this effect, resulting in a smaller negative membrane
potential. We also found that replacing 𝑁𝑎ା ions in the inner region by 𝐾ା depolarizes the
membrane (∆𝑉௠ > 0), whereas replacing by 𝐶𝑎ଶା polarizes the membrane. These divergent effects
arise from variations in the strength of cation-lipid interactions and are correlated with changes in
lipid chain order and head group orientation.


Email Address of Submitting Author


Beihang University



ORCID For Submitting Author


Declaration of Conflict of Interest

No Conflict of Interest

Version Notes

The following article has been submitted to The Journal of Chemical Physics (JCP).