Melittin–Lipid interaction: A comparative study using liposomes, micelles and bilayerdisks

Abstract

Comparison of melittin interaction with liposomes, bilayer disks and micelles showed that melittin binding to lipid aggregates is largely dictated by the amount of highly curved areas in the aggregates. The PEG-stabilised bilayer disks were characterised by a combination of small angle neutron scattering, cryo-transmission electron microscopy and dynamic light scattering. Importantly, the theoretically foreseen partial segregation of the lipid components, important for maintaining the structure of the bilayer disk, was confirmed. Steady state fluorescence spectroscopy indicated that melittin mainly resides at the rim of the bilayer disks. Results of the present study help increase the understanding of the mechanisms behind, and the physico-chemical factors affecting, melittin-lipid interaction. We suggest that bilayer disks, due to their stable structure, constitute interesting vehicles for transport of peptides that have high propensity to associate with lipid surfaces of high curvature.

PEG-stabilized lipid disks as carriers for amphiphilic antimicrobial peptides

“…In all experiments the free melittin concentration was kept as low as possible while still allowing maximum melittin loading on the disks. Binding isotherm data collected by Lundquist et al [9] was used to determine the optimal melittin to lipid ratio. The peptide to lipid ratio in the disks was 0.041 giving a free melittin concentration of 1.3 µM.…”

“…Furthermore, the maximum loading capacity of the disks is superior to that of liposomes. In the case of melittin, previous studies indicate that the maximum peptide to lipid ratio that can be achieved is about ten times higher in disks than in liposomes [9]. Importantly, under conditions corresponding to maximum binding the disks remain intact and structurally unperturbed whereas liposomes under the same conditions rupture and display severe structural alterations [14].…”

“…In the present study the potential of a novel vehicle, the polyethylene glycol (PEG)-stabilized lipid disk, as carrier for peptide drugs is evaluated. The PEG-stabilized lipid disk is a nanosized flat circular lipid bilayer surrounded by a highly curved rim [9]. The disks are obtained by mixing lipids that spontaneously form bilayer structures with close to zero curvature with micelle-forming PEG-lipids, i.e., lipids that have a bulky polymer chain covalently attached to their polar head-group.…”

Immobilized lipodisks as model membranes in high-throughput HPLC-MS analysis

“…The latter, so called PEG-lipids, are micelle-forming compounds and therefore prefer aggregates of high positive curvature. The components in the lipodisks partially segregate and the PEGylated lipids are predominantly found at the disk rim (21). The size of the disks can be varied by alteration of the PEG-lipid content (17,22).…”

Cryo Imaging of Life Science and Soft Matter Samples by a State of the Art 120 kV EFTEM

“…In particular, many studies using CryoTEM on liposomes ( Fig. 2) used as carrier for drugs have been presented ( [1], [2], [3], [4]). CryoTEM supports studies of structural and functional properties of bio-inspired surfactants for controlled fabrication of sophisticated nano-carriers and gets growing importance in pharmaceutical applications to exploit lipids as models in nanotechnology.…”