Interaction Of Poloxamers With Lipid Bilayer: Molecular Dynamics Simulations Using United Atom And Coarse-Grained Force Fields

Poloxamers are triblock copolymers containing a hydrophilic polyethylene oxide block on either side of a hydrophobic polypropylene oxide block (PEO-PPO-PEO). Poloxamer molecules of different block lengths are used for various purposes: to facilitate gene/drug delivery, as an emulsifying agents and/or as agents helping in healing of damaged cell membranes. To understand their actions on a molecular level, we performed a series of molecular dynamic simulations using a modified united atom (UA) and a coarse-grained force fields for poloxamers. These force fields correctly reproduce various experimental properties and observations, like the radii of gyration, and distributions of poloxamers at the hydrophilic/hydrophobic interface. We considered two poloxamers of interest to us; one is P85 (PEO26PPO40PEO26) which is slightly hydrophobic, and another is P188 (PEO80PPO27PEO80) which is hydrophilic. Our results show that in both cases the hydrophobic PPO chain of the poloxamer inserts into the DMPC lipid bilayer, whereas the PEO chain mostly interacts with the lipid headgroups. We also studied the properties of P85 and P188 micelles in water and at the water-lipid bilayer interface using coarse-grained simulations. P85 micelle (aggregation number = 60) assumes a spherical shape, whereas P188 micelle (aggregation umber = 21) is slightly distorted from a spherical shape. No translocation of poloxamers through the bilayer was observed during the 5 µs simulation of a single poloxamer or a micelle containing poloxamers. However, we observed that the P85 micelle adsorbed on a lipid bilayer survace curves the bilayer significantly. Our simulations also showed that P188 micelle helps to close pores in the lipid bilayer.