Coarse-Grained Model for PEGylated Lipids: Effect of PEGylation on the Size and Shape of Self-Assembled Structures

Lee, Hwankyu; Pastor, Richard W.

doi:10.1021/jp2020148

Cited by 105 publications

(153 citation statements)

References 54 publications

Supporting

Mentioning

136

Contrasting

Order By: Relevance

“…The MARTINI PEO/PEG model predicted the size, diffusivities, hydrodynamics, end-to-end distances, and the distributions of bond lengths, angles, and dihedrals, all of which were close to those from all-atom simulations and experiments [43]. In Figure 1, mixtures of lipids and PEGylated lipids in water self-assemble to liposomes, bicelles, and micelles at the expected ratios of lipids and PEGylated lipids [44,45], showing that the aggregate size decreases with increasing PEGylated-lipid concentration, in qualitative agreement with experiment. Recently, this CG model was reparameterized by the Monticelli group, which has an increased time step, while maintaining the accurate prediction of PEG conformation [46].…”

Section: Development Of All-atom and Coarse-grained Peo/peg Force Fieldssupporting

confidence: 59%

Molecular Modeling of PEGylated Peptides, Dendrimers, and Single-Walled Carbon Nanotubes for Biomedical Applications

Lee

2014

Polymers

Self Cite

View full text Add to dashboard Cite

Polyethylene glycol (PEG) has been conjugated to many drugs or drug carriers to increase their solubility and circulating lifetime, and reduce toxicity. This has motivated many experimental studies to understand the effect of PEGylation on delivery efficiency. To complement the experimental findings and uncover the mechanism that cannot be captured by experiments, all-atom and coarse-grained molecular dynamics (MD) simulations have been performed. This has become possible, due to recent advances in simulation methodologies and computational power. Simulations of PEGylated peptides show that PEG chains wrap antimicrobial peptides and weaken their binding interactions with lipid bilayers. PEGylation also influences the helical stability and tertiary structure of coiled-coil peptides. PEGylated dendrimers and single-walled carbon nanotubes (SWNTs) were simulated, showing that the PEG size and grafting density significantly modulate the conformation and structure of the PEGylated complex, the interparticle aggregation, and the interaction with lipid bilayers. In particular, simulations predicted the structural transition between the dense core and dense shell of PEGylated dendrimers, the phase behavior of self-assembled complexes of lipids, PEGylated lipids, and SWNTs, which all favorably compared with experiments. Overall, these new findings indicate that simulations can now predict the experimentally observed structure and dynamics, as well as provide atomic-scale insights into the interactions of PEGylated complexes with other molecules.

show abstract

Section: Development Of All-atom and Coarse-grained Peo/peg Force Fieldssupporting

confidence: 59%

Molecular Modeling of PEGylated Peptides, Dendrimers, and Single-Walled Carbon Nanotubes for Biomedical Applications

Lee

2014

Polymers

Self Cite

View full text Add to dashboard Cite

show abstract

“…It seems, however, somewhat less probable that PB-PEO exerts the same effect on the self-assembly and permeability properties of POPC. Furthermore, for liposomes, addition of PEG-ylated lipids (>10 mol %) leads to micelle formation [34,35]. In our PB-PEO/POPC system, addition of 25%, 50% or 75% of PB-PEO did not result in micelle formation.…”

Section: Encapsulation Efficiency and Membrane Permeabilitymentioning

confidence: 66%

Hybrid, Nanoscale Phospholipid/Block Copolymer Vesicles

et al. 2013

View full text Add to dashboard Cite

Hybrid phospholipid/block copolymer vesicles, in which the polymeric membrane is blended with phospholipids, display interesting self-assembly behavior, incorporating the robustness and chemical versatility of polymersomes with the softness and biocompatibility of liposomes. Such structures can be conveniently characterized by preparing giant unilamellar vesicles (GUVs) via electroformation. Here, we are interested in exploring the self-assembly and properties of the analogous nanoscale hybrid vesicles (ca. 100 nm in diameter) of the same composition prepared by film-hydration and extrusion. We show that the self-assembly and content-release behavior of nanoscale polybutadieneb-poly(ethylene oxide) (PB-PEO)/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) hybrid phospholipid/block copolymer vesicles can be tuned by the mixing ratio of the amphiphiles. In brief, these hybrids may provide alternative tools for drug delivery purposes and molecular imaging/sensing applications and clearly open up new avenues for further investigation. OPEN ACCESSPolymers 2013, 5 1103

show abstract

“…20,21 The MARTINI force field has been parameterized and applied previously to the simulation of proteins, peptides, polymers, and polymer-peptide conjugates. [37][38][39][40][41][42] This model is based on the four-to-one mapping with each bead in the coarse-grained model representing four heavy atoms in the atomistic model. The coarse graining of the peptide and macromer is schematically illustrated in Figure 1a.…”

Section: Simulation Methodsmentioning

confidence: 99%

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Moeinzadeh

Barati²,

Sarvestani³

et al. 2015

Tissue Engineering Part A

View full text Add to dashboard Cite

An attractive approach to reduce the undesired side effects of bone morphogenetic proteins (BMPs) in regenerative medicine is to use osteoinductive peptide sequences derived from BMPs. Although the structure and function of BMPs have been studied extensively, there is limited data on structure and activity of BMP-derived peptides immobilized in hydrogels. The objective of this work was to investigate the effect of concentration and hydrophobicity of the BMP-2 peptide, corresponding to residues 73-92 of the knuckle epitope of BMP-2 protein, on peptide aggregation and osteogenic differentiation of human mesenchymal stem cells encapsulated in a polyethylene glycol (PEG) hydrogel. The peptide hydrophobicity was varied by capping PEG chain ends with short lactide segments. The BMP-2 peptide with a positive index of hydrophobicity had a critical micelle concentration (CMC) and formed aggregates in aqueous solution. Based on simulation results, there was a slight increase in the concentration of free peptide in solution with 1000-fold increase in peptide concentration. The dose-osteogenic response curve of the BMP-2 peptide was in the 0.0005-0.005 mM range, and osteoinductive potential of the BMP-2 peptide was significantly less than that of BMP-2 protein even at 1000-fold higher concentrations, which was attributed to peptide aggregation. Further, the peptide or PEG-peptide aggregates had significantly higher interaction energy with the cell membrane compared with the free peptide, which led to a higher nonspecific interaction with the cell membrane and loss of osteoinductive potential. Conjugation of the BMP-2 peptide to PEG increased CMC and osteoinductive potential of the peptide whereas conjugation to lactide-capped PEG reduced CMC and osteoinductive potential of the peptide. Experimental and simulation results revealed that osteoinductive potential of the BMP-2 peptide is correlated with its CMC and the free peptide concentration in aqueous medium and not the total concentration.

show abstract

Coarse-Grained Model for PEGylated Lipids: Effect of PEGylation on the Size and Shape of Self-Assembled Structures

Cited by 105 publications

References 54 publications

Molecular Modeling of PEGylated Peptides, Dendrimers, and Single-Walled Carbon Nanotubes for Biomedical Applications

Molecular Modeling of PEGylated Peptides, Dendrimers, and Single-Walled Carbon Nanotubes for Biomedical Applications

Hybrid, Nanoscale Phospholipid/Block Copolymer Vesicles

Experimental and Computational Investigation of the Effect of Hydrophobicity on Aggregation and Osteoinductive Potential of BMP-2-Derived Peptide in a Hydrogel Matrix

Contact Info

Product

Resources

About