Thermal gating in lipid membranes using thermoresponsive cyclic peptide-polymer conjugates

The partition and self-assembly of a new generation of cyclic peptide-polymer conjugates into well-defined phospholipid trans-bilayer channels is presented. By varying the structural parameters of the cyclic peptide-polymer conjugates through the ligation of hydrophobic and hydrophilic polymers, both the structure of the artificial channels using large unilamellar vesicle assays and the structural parameters required for phospholipid bilayer partitioning are elucidated. In addition, temperature was used as an external stimulus for the modulation of transbilayer channel formation without requiring the redesign and synthesis of the cyclic peptide core. The thermoresponsive character of the cyclic peptide-polymer conjugates lays the foundation for on-demand control over phospholipid transmembrane transport, which could lead to viable alternatives to current transport systems that traditionally rely on endocytic pathways.