(556c) Design of 3-Helix Micelles with Tailorable Sizes and Shapes

Hierarchical self-assembled micelles from amphiphilic hybrid 3 helix peptide-polymer-lipid conjugates have shown great promise as nanocarriers in delivering therapeutic compounds in a targeted fashion. In order to realize the vast therapeutic potential of these micellar nanocarriers as well as the purpose of penetrating deep tissue or other biological barriers, there is a need to understand how PEG conjugation affects the micelle shape and size as well as self-assembly mechanisms. Atomistic molecular dynamics (MD) simulations of the self-assembly behavior in such length scales is challenging, which necessitates the development of a simpler coarse-grained (CG) model. First, we use a CGMD model based on the dissipative particle dynamics (DPD) technique to reveal the internal structure of 3-helix micelle and the behavior of conjugated PEG chains [1]. Next, we study the self-assembly patterns of the amphiphiles with different PEG molecular weights and conjugation positions on peptide bundles by considering the micelles aggregation number in the simulation box. We discover that the micelle size and stability is dictated by a competition between the entropy of confined PEG chains in the conjugation state, as well as intermolecular interactions among PEG chains that promote cohesion between neighboring amphiphiles. Furthermore, a computational phase diagram that can be used to design 3-helix micelles is conducted. This work opens pathways to control the morphology of self-assembled micelles with expectable and tailorable size, shape and stability as nanocarriers in drug delivery and other applications.

REFERENCES

[1] Ang, J.; Ma, D.; Lund, R.; Keten, S.; Xu, T. Internal structure of 3-helix micelle revealed by small-angle neutron scattering and coarse-grained MD simulation (In submission).