Cell Membrane Derived Platform To Study Virus Binding Kinetics and Diffusion with Single Particle Sensitivity
Artikel i vetenskaplig tidskrift, 2018

Discovery and development of new antiviral therapies essentially rely on two key factors: an in-depth understanding of the mechanisms involved in viral infection and the development of fast and versatile drug screening platforms. To meet those demands, we present a biosensing platform to probe virus-cell membrane interactions on a single particle level. Our method is based on the formation of supported lipid bilayers from cell membrane material. Using total internal reflection fluorescence microscopy, we report the contribution of viral and cellular components to the interaction kinetics of herpes simplex virus type 1 with the cell membrane. Deletion of gC, the main viral attachment glycoprotein, or deletion of heparan sulfate, an attachment factor on the cell membrane, leads to an overall decrease in association of virions to the membrane and faster dissociation from the membrane. In addition to this, we perform binding inhibition studies using the antiviral compound heparin to estimate its IC50 value. Finally, single particle tracking is used to characterize the diffusive behavior of the virus particles on the supported lipid bilayers. Altogether, our results promote this platform as a complement to existing bioanalytical assays, being at the interface between simplified artificial membrane models and live cell experiments.

single particle tracking

biomimetic sensing platform

herpes simplex virus

supported lipid bilayers

virus−membrane interactions

binding kinetics

Författare

Nadia Peerboom

Chalmers, Fysik, Biologisk fysik

Eneas Schmidt

Chalmers, Fysik, Biologisk fysik

Edward Trybala

Göteborgs universitet

Stephan Block

Freie Universität Berlin

Tomas Bergström

Göteborgs universitet

Hudson Pace

Chalmers, Fysik, Biologisk fysik

Marta Bally

Umeå universitet

Chalmers, Fysik, Biologisk fysik

ACS Infectious Diseases

2373-8227 (eISSN)

Vol. 4 6 944-953

Bioanalytiska verktyg för multivalenta interaktioner: från cell membranets dynamik på nanoskala till virusinfektion

Vetenskapsrådet (VR), 2013-01-01 -- 2016-12-31.

Ämneskategorier

Cellbiologi

Biofysik

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1021/acsinfecdis.7b00270