(361h) Interaction of PCL Based Nanopolymeric Micelles with Model Lipid Bilayers Via Explicit and Implicit Solvent Coarse-Grained Simulations

PCL based nanoparticles,
typically formed from amphiphilic block copolymers consisting of water-soluble
chains such as PEG, and functionalized with various ligands and other functional
groups, are widely used in drug delivery applications. Nanopolymeric
micelles formed from PEG-b-PCL copolymers have shown to evade the
reticuloendothelial system, thereby providing improved circulation time to the
nanocarriers, resulting in potential benefits to the betterment of human
health. However, interaction of these nanocarriers with the cell membrane plays
a crucial role in their endocytosis, potentially providing insights into their
design and chemical make-up.

In this study, we perform
coarse-grained molecular dynamics simulations to understand the interaction of micelles
formed from MePEG-b-PCL copolymers, with a simple model DOPC lipid bilayer. Using
existing models in the MARTINI coarse-grained force field for MePEG and PCL, we
investigate the interaction of small micelles with a DOPC bilayer, in an
explicit solvent setup. We found that the degree of hydrophobicity plays a
crucial role in the interaction of the micelles with the bilayer, and also that
the bilayer induced a change in morphology of the core-shell micelles to Janus
particles during the internalization process. Key structural properties of the
bilayer such as membrane thickness, lipid order parameter etc. were found to be
largely unaffected during the internalization process, although dynamic and
mechanical properties showed more changes when the bilayer was perturbed by the
micelles. To explore larger spatio-temporal scales,
the transferability of the developed models for MePEG and PCL to an implicit
solvent setup using the ‘Dry MARTINI’ force field is also investigated. This
paves the way for understanding the interactions of nanoparticles with large
bilayers, at a much lower computational cost.

Fig 1. Bilayer induced change
in morphology of core-shell micelles to Janus particles (color codes:
green-MePEG, red-PCL, blue- DOPC; only the head groups are shown for better
clarity)