Effects of Membrane Defects and Polymer Hydrophobicity on Networking Kinetics of Vesicles

The kinetics of clustering unilamellar vesicles induced by inverse Pluronics [poly(propylene oxide)_m-poly(ethylene oxide)_n-poly(propylene oxide)_m, PO_m-EO_n-PO_m] was investigated via experiments and molecular dynamic simulations. Two important factors for controlling the networking kinetics are the membrane defects, presumably located at the interfacial region between two lipid domains induced by acyl chain mismatch, and the polymer hydrophobicity. As expected, the clustering rate increases significantly with increasing bilayer defects on the membrane where the insertion of PPO is likely to take place because of the reduced energy barrier for the insertion of PO. The hydrophobic interaction between the PO blocks and membranes with the defects region dictates the "anchoring" kinetics, which is controlled by the association-dissociation of PO with the lipid membrane. As a result, the dependence of clustering rate on polymer concentration is strongly influenced by the hydrophobicity of the PO blocks. Nevertheless, longer PO blocks show stronger association with the membrane, resulting in faster consumption of the "active" sites made of these defect regions (causing mostly "invalid" insertions) with increasing polymer concentration, hence inhibiting the formation of large networking clusters, while shorter PO blocks undergo more frequent association with/dissociation from the defects, allowing continuous formation of larger clusters with increasing polymer concentration. This study provides important insights into how the organization and dynamics of a biomembrane influence its interaction with foreign amphiphilic molecules.