Year: 2026
Type: article
Abstract: 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.
Source: RSC Advances
DOI: 10.1039/d6ra06238e
Authors: Eden J. Gage, Philip C. Biggin
Institution: University of Oxford
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $1,042
Funder: University of Oxford
OpenAlex ID: W7167895102