The study of detailed mechanism of polymer/ biological membrane interactions using computer simulation
Zusammenfassung der Projektergebnisse
Understanding the interactions of biocompatible block polymers with biological interfaces and biological molecules has important technological applications in industry and in nanomedicine. In particular, triblocked polymer based on polyethylenoxide (PEO) and polypropilenoxyde (PPO), are broadly used for biotechnological and biomedical applications. The project aimed to study using molecular dynamics simulations at atomistic and coarsegrained scale the interactions between these polymers (as single chains and micelles) with biological interfaces and small molecules. The results of the project have provided accurate models at different level of scale of ether-based linear polymers that have been used to study the mechanism of interaction and percolation with biological interfaces. The outcome of the project can be summarized in these four main points. 1) We have developed novel computational models of ether-based polymers PEO, PPO and PEO-PPO-PEO triblock copolymers. The models have been tested against physical (radius of gyration), dynamical (diffusion coefficients) and thermodynamics (solvation free energies, 1-octanol/water partition coefficients) experimental properties of the polymer in water and non-aqueous solvents. 2) The interactions of the new model polymer with artificial (n-heptane/water) and biological (water/DMPC, lipid bilayer) interfaces have been investigated. The study has evidenced the thermodynamics tendency of the hydrophobic part of the polymer to be located in the hydrophobic phase or in the lipid bilayer and the hydrophilic part to fluctuate in the water phase. In addition, the percolation free energy barriers have been estimated for small polymeric chains providing a quantitative estimation their effect. 3) A model of drug molecule Curcumin was parameterized and it was used to study its encapsulation in block copolymers. In the case of triblock polymer Pluronics® P85, the hydrophobic PPO chains wrap around the Curcumin molecule leaving the PEO parts exposed and thus resulting in better solvation and stability of the drug molecule in water. This also affects the mobility of the drug molecule by decreasing its diffusion coefficient. The observed condensing polymer aggregate could be the first step to form the larger micelle observed in the experimental study reported in literature. 4) The results of the atomistic studies have been used to parameterize coarse-grained models of triblock copolymers, which allowed extending the study on large-scale phenomena. In particular, we studied the interaction of single chains up to complete polymeric micelle with biological membrane. The results were in good agreement with the available experimental results and they suggest that the process proceed by a twostage mechanism. Finally, using a recently developed Self Consistent density Field method, simulation studies of Pluronics micelles formation and their interaction with DPPC lipid bilayers were accomplished. The results of these simulations evidenced a possible scenario of micelle dissolution at the bilayer surface that consists in a progressive diffusion of single Pluronics chains in contact with the interface from the micelle into the bilayer. These results represent the first comprehensive study of these systems at multi-scale level. They provide details that complement experimental results for better understand drug delivery systems based on these types of polymers. Furthermore, the polymer models can be used to further extend this study to analysis the interaction with other biological system (proteins and nucleic acids) and small molecules (drugs) as well as to consider the effect of the corresponding ether-based branched polymers.
Projektbezogene Publikationen (Auswahl)
- Hybrid Particle-Field Coarse-Grained Models for Biological Phospholipids. JTCC, 7 (9), 2947–2962 (2011)
A. De Nicola, Y. Zhao, T. Kawakatsu, D. Roccatano and G. Milano
- Structure and dynamics of 1,2-dimethoxyethane and 1,2-dimethoxypropane in aqueous and non-aqueous solutions: A molecular dynamics study. J. Chem. Phys., 135, 164501, (2011). Cover page
S. Hezaveh, S. Samanta, G. Milano, D. Roccatano
- Molecular dynamics simulation study of solvent effects on conformation and dynamics of polyethylene oxide and polypropylene oxide chains in water and in common organic solvents. J. Chem. Phys. 136, 124901, (2012)
S. Hezaveh, S. Samanta, G. Milano, D. Roccatano
(Siehe online unter https://doi.org/10.1063/1.3694736) - Theoretical Study of the Interaction of 1,2-dimethoxyethane and 1,2-dimethoxypropane with Biological Interfaces. JPC B, 116 (17), 5141–5151 (2012). Cover page
Samanta, S. Hezaveh, G. Milano, D. Roccatano
- Understanding the Interaction of Block Copolymers with DMPC Lipid Bilayer Using Coarse-Grained Molecular Dynamics Simulations. J. Phys. Chem B. 116 (49), 14333–14345, (2012)
S. Hezaveh, A. De Nicola, G. Milano, D. Roccatano
(Siehe online unter https://doi.org/10.1021/jp306565e) - Validation of a Hybrid Particle-Field Coarse-Grained Model for DPPC in Non-Lamellar Phases. Theo. Chem. Act. 131, 1167, (2012)
De Nicola, Y. Zhao, T. Kawakatsu, D. Roccatano and G. Milano
- „Study of the interaction Mechanisms of Block Copolymers with Biological Interfaces”. PhD Thesis
Samira Hezaveh
- „Theoretical Study of the Interaction of Amphiphilic Block Co- Polymers with Biological Interfaces and Small Molecules." PhD Thesis
Susruta Samanta
- Interaction of Curcumin with PEO-PPO-PEO block copolymers: A molecular dynamics study. J. Phys. Chem. B, 117 (11), 3250–3257, (2013)
S. Samanta, D. Roccatano
(Siehe online unter https://doi.org/10.1021/jp309476u)
