| AVS 58th Annual International Symposium and Exhibition | |
| Biomaterial Interfaces Division | Tuesday Sessions |
| Session BI-TuA |
| Session: | Protein-Membrane Interactions |
| Presenter: | Marta Bally, Chalmers University of Technology, Sweden |
| Authors: | M. Bally, Chalmers University of Technology, Sweden G. Larson, University of Gothenburg, Sweden F. Höök, Chalmers University of Technology, Sweden |
| Correspondent: | Click to Email |
The determining initial step of viral infection is mediated by highly specific recognition events between the viral shell and ligands on the host cell surface. Detailed understanding of virus-membrane interactions is therefore of central importance to the development of new antiviral therapies, new vaccines and high-performance diagnostics platforms. In this context, assays based on cell-membrane mimics have a considerable potential, as they offer the possibility to study interactions between controlled ligand mixtures with surface-sensitive techniques, while presenting the ligand in a more native configuration. Potentially relevant characteristics such as membrane fluidity, ligand mobility and their ability to organize into microdomains can be preserved [1].
In this work we investigate the interactions between norovirus capsids and phospholipid bilayers containing glycosphingolipids (GSL). The norovirus is well known as the major causative agent of acute viral gastroenteritis, but its human target cells and the precise mechanism for viral entry are still poorly understood.
In a first example, we identify galctosylceramide - a major glycosphingolipid in the small intestine- as a ligand for Norovirus-like particles (VLP) from the Dijon strain. Quartz Crystal Microbalance and Atomic Force Microscopy studies on GalCer-containing supported lipid bilayers reveal that a clustered arrangement of the glycosphingolipids plays a crucial role in promoting a firm attachment of the pathogen to the lipidic membrane, most likely via the establishment of multiple contacts between the particle and the membrane [2].
We further investigated the interaction between individual fluorescent GSL liposomes and surface immobilized VLPs with single virus particle sensitivity. Besides representing the ultimate sensitivity for diagnostics purposes, our method makes it possible to study weak interactions. Kinetics analysis of vesicle residence times over large time scales reveals a highly heterogeneous behavior and yields information on multivalency, on the presence of domains and the role of cell-membrane curvature.
As exemplified here, simplified membrane models have a unique potential in providing fundamental understanding on the contribution of individual components to complex biological processes [3].
[1] Bally et al. "Liposome and Lipid Bilayer Arrays Towards Biosensing Applications", SMALL, 2010.
[2] Bally et al. "Interaction of Single Virus-like Particles with Vesicles Containing Glycosphingolipids", submitted.
[3] Bally et al. "Norovirus GII.4 virus-like particles recognize galactosylceramides in microdomains of planar supported lipid bilayers", submitted.