Binding of amphiphilic and triphilic block copolymers to lipid model membranes: the role of perfluorinated moieties

Abstract

A novel class of symmetric amphi-and triphilic (hydrophilic, lipophilic, fluorophilic) block copolymers has been investigated with respect to their interactions with lipid membranes. The amphiphilic triblock copolymer has the structure PGMA 20 -PPO 34 -PGMA 20 (GP) and it becomes triphilic after attaching perfluoroalkyl moieties (F9) to either end which leads to F 9 -PGMA 20 -PPO 34 -PGMA 20 -F 9 (F-GP). The hydrophobic poly(propylene oxide) (PPO) block is sufficiently long to span a lipid bilayer. The poly(glycerol monomethacrylate) (PGMA) blocks have a high propensity for hydrogen bonding. The hydrophobic and lipophobic perfluoroalkyl moieties have the tendency to phase segregate in aqueous as well as in hydrocarbon environments. We performed differential scanning calorimetry (DSC) measurements on polymer bound lipid vesicles under systematic variation of the bilayer thickness, the nature of the lipid headgroup, and the polymer concentration. The vesicles were composed of phosphatidylcholines (DMPC, DPPC, DAPC, DSPC) or phosphatidylethanolamines (DMPE, DPPE, POPE). We showed that GP as well as F-GP binding have membrane stabilizing and destabilizing components.PPO and F9 blocks insert into the hydrophobic part of the membrane concomitantly with PGMA block adsorption to the lipid headgroup layer. The F9 chains act as additional membrane anchors. The insertion of the PPO blocks of both GP and F-GP could be proven by 2D-NOESY NMR spectroscopy. By fluorescence microscopy we show that F-GP binding increases the porosity of POPC giant unilamellar vesicles (GUVs), allowing the influx of water soluble dyes as well as the translocation of the complete triphilic polymer and its accumulation at the GUV surface. These results open a new route for the rational design of membrane systems with specific properties.

Mixed Hybrid Lipid/Polymer Vesicles as a Novel Membrane Platform

“…When synthetic polymers interact with lipid membranes, the final morphology is determined by the charge, size, and molar ratio of the interacting components . In general, a mixture of polymers with lipids represents a polyphilic system, where several (im)miscibility effects compete with each other, such as polymer with polymer and polymer with the hydrophobic lipid tail or with the hydrophilic lipid head group. Furthermore, the ordering phenomena of polymers (macrophase segregation) and lipids (lyotropic phase behavior) comes into competition.…”

Conformational Space of a Polyphilic Molecule with a Fluorophilic Side Chain Integrated in a DPPC Bilayer

“…One way of modification is the introduction of trans‐membrane molecules into the lipid bilayer. In our case, we use a special type of recently synthesized polyphilic trans‐membrane molecules …”

“…Several variations of the hydrophilic end groups and side chains of the polyphile have been synthesized and inserted into phospholipid bilayers, to tune aggregation behavior and order parameters of these additives . In our work, we focus on a simple yet representative molecule (see Fig.…”

Cluster Formation of Polyphilic Molecules Solvated in a DPPC Bilayer

“…Polyphilic molecules can be used to modify the phase transitions temperature of a lipid bilayer [11] and also serve as a drug delivery agent [12,13]. Furthermore, they cause effects like compression or stretching of bilayer systems which was recently shown [11,14,15,16,17,18]. Fluorocarbon compounds are also studied for influencing the metabolism of rats [19,20] and for in vitro synthesis of lipid bilayer proteins [21].…”