Self-assembly of glycerol monooleate with the antimicrobial peptide LL-37: a molecular dynamics study.

Over the past decade, the rapid increase in the incidence of antibiotic-resistant bacteria has promoted research towards alternative therapeutics such as antimicrobial peptides (AMPs), but their biodegradability limits their application. Encapsulation into nanocarriers based on the self-assembly of surfactant-like lipids is emerging as a promising strategy for the improvement of AMPs' stability and their protection against degradation when in biological media. An in-depth understanding of the interactions between the structure-forming lipids and AMPs is required for the design of nanocarriers. This in silico study, demonstrates the self-assembly of the amphiphilic lipid glycerol monooleate (GMO) with the antimicrobial peptide LL-37 into nanocarriers on the molecular scale. Molecular dynamics (MD) simulations show the formation of direct micelles, with either one or two interacting LL-37, and vesicles in this two-component system in agreement with experimental results from small-angle X-ray scattering studies. The hydrophobic contacts between LL-37 and GMOs in water appear responsible for the formation of these nanoparticles. The results also suggest that the enhanced antimicrobial efficiency of LL-37 in these nanocarriers that was previously observed experimentally can be explained by the availability of its side chains with charged amino acids, an increase of the electrostatic interaction and a decrease of the peptide's conformational entropy upon interacting with GMO. The results of this study contribute to the fundamental understanding of lipid-AMP interactions and may guide the comprehensive design of lipid-based self-assembled nanocarriers for antimicrobial peptides.

Formation of highly ordered liquid crystalline coatings - an in situ GISAXS study.

Functional coatings based on self-assembled lyotropic liquid crystals have the potential for applications such as biosensing, drug delivery and nanotemplating. Here we demonstrate the design and in-depth characterization of glycerol monooleate based liquid crystalline coatings on silicon wafers using drop casting and spin coating techniques. In situ time-resolved grazing incidence small angle X-ray scattering (GISAXS) measurements were used to monitor the coating formation and its response to increasing relative humidity conditions between 5 and 100%. Additional atomic force microscopy (AFM) measurements were applied to visualize the coating nanostructure. Structural transformations through ordered intermediate phases to the sponge- and lamellar phase were observed during ethanol evaporation. Relative humidity dependent GISAXS results revealed gradual phase transitions from the lamellar via the gyroid type cubic phase to the diamond type bicontinuous cubic structure between 5 and 100% relative humidity. The detailed insights into the formation and transformation of the coating nanostructures in this system may provide essential knowledge for the comprehensive design of functional nanostructured surfaces in biomedical applications.

Direct monitoring of lipid transfer on exposure of citrem nanoparticles to an ethanol solution containing soybean phospholipids by combining synchrotron SAXS with microfluidics.

Lipid exchange among citrem nanoparticles and an ethanol micellar solution containing soy phosphatidylcholine was investigated in situ by coupling small angle X-ray scattering with a microfluidic device. The produced soy phosphatidylcholine/citrem nanoparticles have great potential in the development of hemocompatible nanocarriers for drug delivery.