Receptor Concentration and Diffusivity Control Multivalent Binding of Sv40 to Membrane Bilayers
PLoS Comput Biol. 2013-11-14; 9(11): e1003310
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Szklarczyk OM(1), González-Segredo N, Kukura P, Oppenheim A, Choquet D,
Sandoghdar V, Helenius A, Sbalzarini IF, Ewers H.
(1)MOSAIC Group, Institute of Theoretical Computer Science and Swiss Institute of
Bioinformatics, ETH Zurich, Zurich, Switzerland ; Laboratory of Physical
Chemistry, ETH Zurich, Zurich, Switzerland.
Incoming Simian Virus 40 particles bind to their cellular receptor, the
glycolipid GM1, in the plasma membrane and thereby induce membrane deformation
beneath the virion leading to endocytosis and infection. Efficient membrane
deformation depends on receptor lipid structure and the organization of binding
sites on the internalizing particle. To determine the role of receptor diffusion,
concentration and the number of receptors required for stable binding in this
interaction, we analyze the binding of SV40 to GM1 in supported membrane bilayers
by computational modeling based on experimental data. We measure the diffusion
rates of SV40 virions in solution by fluorescence correlation spectroscopy and of
the receptor in bilayers by single molecule tracking. Quartz-crystal microbalance
with dissipation (QCM-D) is used to measure binding of SV40 virus-like particles
to bilayers containing the viral receptor GM1. We develop a phenomenological
stochastic dynamics model calibrated against this data, and use it to investigate
the early events of virus attachment to lipid membranes. Our results indicate
that SV40 requires at least 4 attached receptors to achieve stable binding. We
moreover find that receptor diffusion is essential for the establishment of
stable binding over the physiological range of receptor concentrations and that
receptor concentration controls the mode of viral motion on the target membrane.
Our results provide quantitative insight into the initial events of virus-host
interaction at the nanoscopic level.