title: Activity of synthetic ion channels is influenced by cation-pi interactions with phospholipid headgroups.
abstract: A suite of synthetic hydraphile ion channels has been used to probe the possibility of cation-pi interactions between the channel and the phospholipid bilayer. The hydraphiles selected for this study contained either no sidearm, aliphatic sidearms or aromatic sidearms that varied in electron-richness. An ion selective electrode (ISE) method was used to evaluate the ion transport ability of these hydraphiles across synthetic bilayers. Transport was dependent on sidearm identity. Ion transport activity for the aromatic sidechained compounds was greatest when the sidearms were electron rich and vesicles were prepared from 100% DOPC (trimethylammonium cation headgroup, overall neutral). When the lipid headgroups were made more negative by changing the composition from DOPC to 70 : 30 (w/w) DOPC : DOPA, transport by the aromatic-sidechained channels was reduced. Fluorescence studies showed that when the lipid composition changed, the headgroups experienced a different polarity, suggesting reorientation. The data are in accord with a stabilizing cation-pi interaction between the aromatic sidearm of the hydraphile channel and the ammonium phospholipid headgroup.
authors.affiliation: Department of Molecular Biology & Pharmacology, Washington University School of Medicine, Campus Box 8103, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Weber
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: Elliott
authors.forename: George W
authors.initials: GW
authors.lastname: Gokel
mesh_terms: D002412:Cations; D004583:Electrons; D007473:Ion Channels / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017136:Ion Transport; D017736:Ion-Selective Electrodes; D008051:Lipid Bilayers / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D002412:Cations; D007473:Ion Channels; D008051:Lipid Bilayers; D010743:Phospholipids