Membrane deformation supports ion conduction by the star of David [2]catenane
- 1Structural Bioinformatics and Computational Biochemistry, Department of Biochemistry South Parks Road Oxford OX1 3QU UK
Abstract
Artificial ion channels (AICs) provide synthetic models of membrane transport and have potential therapeutic applications, yet the molecular structures of their conductive membrane states can be difficult to establish experimentally. The (Fe2+)6 Star of David [2]Catenane (SoD) forms highly conductive chloride channels despite a substantial mismatch with bilayer thickness. Here, atomistic molecular dynamics simulations were used to investigate possible membrane–embedded structures and conduction mechanisms of SoD. Pre-embedded, horizontally oriented SoD molecules stabilised hydrated, lipid-lined toroidal pores accompanied by pronounced local membrane deformation, producing continuous hourglass-shaped pathways for chloride permeation. Under applied transmembrane potentials between ±100 mV, SoD catenanes embedded in POPC : cholesterol (2 : 1) bilayers exhibited a conductance of 1.34 ± 0.14 nS, with conductance changes associated with SoD embedding depth and tilt and by lipid occlusion of the pore. Alternative vertically oriented monomers were unstable under the simulated conditions and reoriented towards horizontal configurations, whereas stacked SoD dimers remained conductive. Simulations using pre-formed electropores identified membrane defects as one possible route by which SoD could access embedded configurations, although these simulations do not establish the spontaneous insertion pathway under experimental conditions. Together, the results support a mechanism in which SoD can conduct chloride without itself spanning the bilayer by stabilising a lipid-lined membrane defect. More broadly, this mechanism illustrates how membrane deformation could contribute to conduction by synthetic channels whose molecular dimensions are shorter than the membrane thickness.
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BibTeX
@article{gage2026membrane,
title = {{Membrane deformation supports ion conduction by the star of David [2]catenane}},
author = {Eden J. Gage and Philip C. Biggin},
journal = {RSC advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra06238e},
url = {https://europepmc.org/article/PMC/PMC13730457},
note = {CC BY},
}
RIS
TY - JOUR
TI - Membrane deformation supports ion conduction by the star of David [2]catenane
AU - Eden J. Gage
AU - Philip C. Biggin
PY - 2026
DA - 2026/11/03
JO - RSC advances
DO - 10.1039/d6ra06238e
UR - https://europepmc.org/article/PMC/PMC13730457
AB - Artificial ion channels (AICs) provide synthetic models of membrane transport and have potential therapeutic applications, yet the molecular structures of their conductive membrane states can be difficult to establish experimentally. The (Fe2+)6 Star of David [2]Catenane (SoD) forms highly conductive chloride channels despite a substantial mismatch with bilayer thickness. Here, atomistic molecular dynamics simulations were used to investigate possible membrane–embedded structures and conduction mechanisms of SoD. Pre-embedded, horizontally oriented SoD molecules stabilised hydrated, lipid-lined toroidal pores accompanied by pronounced local membrane deformation, producing continuous hourglass-shaped pathways for chloride permeation. Under applied transmembrane potentials between ±100 mV, SoD catenanes embedded in POPC : cholesterol (2 : 1) bilayers exhibited a conductance of 1.34 ± 0.14 nS, with conductance changes associated with SoD embedding depth and tilt and by lipid occlusion of the pore. Alternative vertically oriented monomers were unstable under the simulated conditions and reoriented towards horizontal configurations, whereas stacked SoD dimers remained conductive. Simulations using pre-formed electropores identified membrane defects as one possible route by which SoD could access embedded configurations, although these simulations do not establish the spontaneous insertion pathway under experimental conditions. Together, the results support a mechanism in which SoD can conduct chloride without itself spanning the bilayer by stabilising a lipid-lined membrane defect. More broadly, this mechanism illustrates how membrane deformation could contribute to conduction by synthetic channels whose molecular dimensions are shorter than the membrane thickness.
SN - 2046-2069
ER -