Effects of the poloxamer?s structure on its interaction with model membranes revealed by molecular dynamics simulations at coarse grain scale

I. WOOD; M.F. MARTINI; M. PICKHOLZ

Bariloche

Conferencia; V Argentinian Conference on Bioinformatics and Computational Biology; 2014

Asociación Argentina de Bioinformática y Biología Computacional

Effects of the poloxamer?s structure on its interaction with model membranes revealed by molecular dynamics simulations at coarse grain scale Irene Wood1;2, M. Florencia Martini1;2, Mónica Pickholz1;2 1-Pharmaceutical Technology Dept, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina, 2-CONICET, Buenos Aires, Argentina. Background. The linear triblock co-polymers belonging to the Pluronic rOclass are composed by a central hydrophobic block of poli(propylene oxide) (PPO) flanked by two identicals hydrophilic blocks of poli(ethylene oxide) (PEO) [1]. These amphiphilic and biocompatible compounds are mainly used for biomedical and pharmaceutical purposes, due to their varied PEO and PPO composition. The poloxamers capability to interact with membranes justifies their applications [2]. Materials and methods. Coarse grained molecular dynamics (MD) simulations have been performed to investigate the interaction between different poloxamers, at their unimer form, with a fully hydrated 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) lipid bilayer, from different initial localizations. Results. We have observed dependence of the unimer behaviors on its structural and physico-chemical features. Most of the studied unimers have shown different conformation depending on the initial condition. For instance, when F127 unimer was set up at the lipid-water interfacial region, adopts a coil structure in which the inner hydrophobic domain (PPO) is surrounded by the outer hydrophilic portion (PEO), which remains in contact with water (Figure 1.A). By the other hand, when F127 was initially placed at the bilayer hydrophobic region, have displayed a trans-membrane conformation, with the PPO block spread into the membrane tail region and the PEO chains water solvated on the both sides of the bilayer (Figure 1.B). Furthermore, the poloxamer L64 behaves in a different way when is compared with F127 and other studied poloxamers. L64 adopts a compact structure at the lipid-water interphase, showing not dependence on initial conditions. Snapshots after 1s for the F127 systems at different initial conditions: A) interphase and B) membrane core. F127 is represented as VDW spheres (PPO in red and PEO in green). POPC (choline in blue, phosphate in magenta, carbonyls in light blue, acyl chains in brown) and water (transparent light blue) are represented as balls and sticks. Conclusion. Our results provide a picture of the conditions determining poloxamer-bilayer interactions. The interaction degree of certain co-polymers with membranes could favor their use as excipients for drug delivery and as indirect inhibitor of transmembrane efflux proteins, whose over-expression is related with multi-drug resistance.