Sub-20 nm Stable Micelles Based on a Mixture of Coiled-Coils: A Platform for Controlled Ligand Presentation.

Ligand-functionalized, multivalent nanoparticles have been extensively studied for biomedical applications from imaging agents to drug delivery vehicles. However, the ligand cluster size is usually heterogeneous and the local valency is ill-defined. Here, we present a mixed micelle platform hierarchically self-assembled from a mixture of two amphiphilic 3-helix and 4-helix peptide-polyethylene glycol (PEG)-lipid hybrid conjugates.

Kinetic Pathway of 3-Helix Micelle Formation.

A subtle but highly pertinent factor in the self-assembly of hierarchical nanostructures is the kinetic landscape. Self-assembly of a hierarchical multicomponent system requires the intricate balance of noncovalent interactions on a similar energy scale that can result in several self-assembly processes occurring at different time scales. We seek to understand the hierarchical assemblies within an amphiphilic 3-helix peptide-PEG-lipid conjugate system in the formation process of highly stable 3-helix micelles (3HMs).

Understanding Peptide Oligomeric State in Langmuir Monolayers of Amphiphilic 3-Helix Bundle-Forming Peptide-PEG Conjugates.

Coiled-coil peptide-polymer conjugates are an emerging class of biomaterials. Fundamental understanding of the coiled-coil oligomeric state and assembly process of these hybrid building blocks is necessary to exert control over their assembly into well-defined structures. Here, we studied the effect of peptide structure and PEGylation on the self-assembly process and oligomeric state of a Langmuir monolayer of amphiphilic coiled-coil peptide-polymer conjugates using X-ray reflectivity (XR) and grazing-incidence X-ray diffraction (GIXD).

Internal Structure of 15 nm 3-Helix Micelle Revealed by Small-Angle Neutron Scattering and Coarse-Grained MD Simulation.

3-Helix micelles (3HM) formed by self-assembly of peptide-polymer conjugate amphiphiles have shown promise as a nanocarrier platform due to their long-circulation, deep tumor penetration, selective accumulation in tumor, and ability to cross the blood-brain barrier (BBB) for glioblastoma therapy. There is a need to understand the structural contribution to the high in vivo stability and performance of 3HM. Using selective deuteration, the contrast variation technique in small-angle neutron scattering, and coarse-grained molecular dynamics simulation, we determined the spatial distribution of each component within 3HM.

Spread Films of Human Serum Albumin at the Air-Water Interface: Optimization, Morphology, and Durability.

It has been known for almost one hundred years that a lower surface tension can be achieved at the air-water interface by spreading protein from a concentrated solution than by adsorption from an equivalent total bulk concentration. Nevertheless, the factors that control this nonequilibrium process have not been fully understood. In the present work, we apply ellipsometry, neutron reflectometry, X-ray reflectometry, and Brewster angle microscopy to elaborate the surface loading of human serum albumin in terms of both the macroscopic film morphology and the spreading dynamics.

Self-assembled 20-nm (64)Cu-micelles enhance accumulation in rat glioblastoma.

There is an urgent need to develop nanocarriers for the treatment of glioblastoma multiforme (GBM). Using co-registered positron emission tomography (PET) and magnetic resonance (MR) images, here we performed systematic studies to investigate how a nanocarrier's size affects the pharmacokinetics and biodistribution in rodents with a GBM xenograft. In particular, highly stable, long-circulating three-helix micelles (3HM), based on a coiled-coil protein tertiary structure, were evaluated as an alternative to larger nanocarriers.

Human serum albumin binding to silica nanoparticles--effect of protein fatty acid ligand.

Neutron reflectivity shows that fatted (F-HSA) and defatted (DF-HSA) versions of human serum albumin behave differently in their interaction with silica nanoparticles premixed in buffer solutions although these proteins have close to the same surface excess when the silica is absent. In both cases a silica containing film is quickly established at the air-water interface. This film is stable for F-HSA at all relative protein-silica concentrations measured.

Resistance of β-casein at the air-water interface to enzymatic cleavage.

X-ray reflectivity from an air-buffer interfacial β-casein monomolecular film placed on a solution of chymosin (renin) showed unexpectedly slow proteolytic cleavage. To understand this, the separate structures of β-casein and chymosin, the presentation of each molecule to the other at the air/liquid interface, and that of their mixtures is reported. At the air/solution interface, the hydrophobicity of the protein molecules causes orientation and some deformation of the conformation.