Physical Chemistry

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

Xubo Lin Beihang University


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),
π‘π‘Žΰ¬Ύ, 𝐾ା and πΆπ‘Žΰ¬Άΰ¬Ύ 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 (βˆ†π‘‰ΰ―  < 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 π‘π‘Žΰ¬Ύ ions in the inner region by 𝐾ା depolarizes the
membrane (βˆ†π‘‰ΰ―  > 0), whereas replacing by πΆπ‘Žΰ¬Άΰ¬Ύ 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.

Version notes

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


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