It is of great importance to interrogate the impact of local environment on the transport of small molecules across lipid bilayers, as they are key to the function and capabilities of eukaryotic cells and liposome-based delivery systems. Herein are described real-time studies of the molecular adsorption and transport kinetics of positively charged small-molecule organic dyes at the surface of liposomes under different buffer and salt conditions, made possible by application of second harmonic generation (SHG). The molecular transport of malachite green (MG) within the liposome bilayer is more rapid in 1,2-dioleoyl-sn-glycero-3-phospho-(1′-rac-glycerol) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPG and DOPS, respectively) liposomes in citrate buffer without added salts, whereas no adsorption or transport of MG is observed in trimethyl quinone-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (QPADOPE) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes. While the transport rate constant increases linearly with concentration of MG for DOPG liposomes, there is much less dependence of the transport rate constant on the concentration of MG in DOPS liposomes. Adsorption site densities and free energies of adsorption are determined using the modified Langmuir adsorption isotherm model by fitting SHG signals resulting from MG addition. The resulting free energy of adsorption for MG to the surface of liposomes is higher in the absence of added salts due to increased electrostatic attractions. However, the corresponding adsorption site densities increase in the presence of salts due to ion-pair formation and decreased repulsions between cationic adsorbates. Comparisons at different citrate buffer and KCl concentrations demonstrate that adsorption and transport of MG in liposomes are influenced by several interrelated factors that include molecular structure of the lipid headgroup, electrostatic interactions between the charged liposome surface and ionic adsorbates and electrolytes, and ion-pair formation. Similar investigations using the structurally similar but more highly charged dicationic dye methyl green point to a lack of its adsorption to and transport within the liposomes, possibly due to a much stronger hydration shell. These findings highlight important considerations for potential liposome-based, drug-delivery applications and the transport of small-molecule drugs across the plasma membrane.

No abstract

No abstract

No abstract

The Air Force Research Laboratory (AFRL) Space Vehicles Directorate has developed the Demonstration and Sciences Experiment (DSX) to research the technologies needed to deploy space assets in the harsh MEO radiation environment. The DSX comprises three basic research experiments: 1) Wave Particle Interaction Experiment, 2) Space Weather Experiment, and 3) Space Environmental Effects Experiment.