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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Monday Speaker Abstracts
19
Artificial Cell Membrane Mimics to Study the Role of the Influenza Virus Matrix Protein
M1 in Virus Budding
David Saletti
1,2
, Birger Eklund
1
, Jens Radzimanowski
3
, Winfried Weissenhorn
3
, Patricia
Bassereau
2
,
Marta Bally
1,2
.
1
Chalmers University of Technology, Gothenburg, Sweden,
2
Institut Curie, Paris, France,
3
Université Joseph Fourier, Grenoble, France.
The influenza virus egresses from its host by deforming the plasma membrane into a bud before
pinching off by membrane fission. The viral matrix protein M1, a protein that forms a layer
underneath the vial membrane connecting it to the viral genetic material, is believed to play an
important role in the virion formation process. Nevertheless, the mechanisms underlying virus
assembly and budding are still poorly understood. In this project, we take advantage of minimal
cell-membrane models to study the interactions between the matrix protein and lipid membranes.
Specifically, we aim at providing fundamental understating on the role of M1 in virus assembly
and egress as well as in virus uncoating during entry.
Giant unilamellar vesicles (GUV) are used to study the protein’s ability to deform membranes
into a bud. Binding studies performed with fluorescently-labelled proteins reveal that M1 alone
is capable of deforming membranes: the interaction leads to membrane inward tubulation,
creating vesicle–enclosed lipid structures greatly enriched in matrix protein.
GUV experiments are further complemented with investigations using supported lipid bilayers
(SLBs) in combination with surface-sensitive techniques. Quartz crystal microbalance
experiments make it possible to characterize the protein’s binding affinity and specificity to
negatively charged membranes. Our data reveal that protein binding is pH, salt and membrane-
charge dependent. Further imaging of the SLB using fluorescence microscopy, surface-enhanced
ellipsometry contrast and atomic force microscopy indicates that the protein can locally recruit
negatively charged lipids, shedding light on the protein’s propensity to self-aggregation at the
bilayer surface.
Taken together, our study illustrate the unique potential of cell membrane mimics in providing
fundamental biophysical insights into the properties of protein-membrane interactions and into
the mechanisms leading to membrane deformation.