Coarse-Grained Molecular Dynamics Modeling of Self-Assembling of Methoxy Poly(ethylene glycol)-Polycaprolactone (MePEG5-PCL9) Nano-Polymeric Micelles

Coarse-grained molecular dynamics modeling of self-assembling of methoxy poly(ethylene glycol)-polycaprolactone (MePEG5-PCL9) nano-polymeric micelles

Joshua Pajak, Abhinav Raman, and Yee C. Chiew

Department of Chemical and Biochemical Engineering

Rutgers University

Piscataway, New Jersey

This study concerns the modeling of the self-assembly of a nano-polymeric micelle formed from amphiphilic macromolecules and its interaction with lipid bilayers using coarse-grained molecular dynamics simulation. The block co-polymer, Methoxy poly(ethylene glycol)-Polycaprolactone (MePEG5-PCL9), belongs to a family of polymers that are often considered to have vital drug delivery applications. Self-assembled nanoparticles can be employed to encapsulate hydrophobic drugs and are a key method of targeted drug delivery. The research objective of this study is to develop coarse-grain molecular force field models for this diblock co-polymer, and to gather crucial information of the statistics and properties of the self-assembled polymer cluster. Additionally, we set out to understand its translocation through a model lipid bilayer.

We applied the MARTINI coarse-grained molecular forcefield to model a large aqueous system of MePEG5-PCL9 polymers. Preliminary simulations were carried out to validate new coarse grained MARTINI parameters for linker groups and dihedral potentials by comparing with all-atom simulations. Coarse-grained molecular dynamics simulations were performed to track the aggregating behavior of the polymers in a water solvated, periodic boundary condition box. Our simulations show that the diblock polymers conglomerated into a single cluster or micelle. The equilibrium cluster in an aqueous solution was then analyzed to gather information on its size and morphology. Using the mean square displacement we were able to calculate the diffusion constant and thus the hydrodynamic radius of the micellar aggregate. Analyzing the ratio of the radius of gyration to the hydrodynamic radius revealed that the morphology of the cluster consists of a dense core of PCL with an outside layer of PEG. The results from the radial distribution of the two blocks (PEG and PCL) match this result. The results obtained from these studies are used to simulate and investigate the interaction and translocation of the self-assembled nano-polymeric micelle through a MARTINI coarse grained DPPC bilayer.