Soft Matter, 2017, Accepted Manuscript
Sivaramakrishnan Ramadurai, Marco Werner, Nigel K.H. Slater, Aaron Martin, Vladimir A. Baulin, Tia Keyes
Deeper understanding of the molecular interactions between polymeric materials and the lipid membrane is important across a range of applications from permeation for drug delivery to encapsulation for immuno-evasion. Using highly fluidic microcavity supported lipid bilayers, we studied the interactions between amphiphilic polymer PP50 and a DOPC lipid bilayer. As the PP50 polymer is pH responsive the studies were carried out at pH 6.5, 7.05 and 7.5, corresponding to fully, and partly protonated (pH 7.05 (pKa)) and the fully ionized states of the polymer respectively. Fluorescence correlation spectroscopy (FCS) using both labelled lipid and polymer revealed the PP50 associates with the bilayer interface across all pHs where its diffusion along the interface is impeded by barriers formed by the polymer itself. Both FCS and electrochemical impedance spectroscopy (EIS) data indicate that the PP50 does not penetrate fully to the bilayer core but rather forms a layer at the bilayer aqueous interface reflected in increased resistance and decreased capacitance of the bilayer on PP50 binding. The extent of these effects and the dynamics of binding are influenced by pH, increasing with decreasing pH. These experimental trends concurred with coarse grained Monte Carlo calculations simulations of the polymer–bilayer interactions wherein a model hydrophilic polymer backbone grafted with side chains of varying hydrophobicity, to mimic the effect of varying pH, was simulated based on the bond fluctuation model with explicit solvent. Simulation showed that with increasing hydrophobicity, the polymer penetrated deeper into the contacting bilayer leaflet of the membrane suppressing, consistent with EIS data, solvent permeation but that the PP50 did not penetrate fully into the hydrophobic core.