Biology subjects

Fortoul, N.

Publications and source records attributed to Fortoul, N..

2 recordsLinked to original sources

bioRxiv2020

Adhesive Contact Between Cylindrical (Ebola) and Spherical (SARS-CoV-2) Viral Particles and a Cell Membrane

A critical event during the process of cell infection by a viral particle is attachment, which is driven by adhesive interactions and resisted by bending and tension. The biophysics of this process has been studied extensively but the additional role of externally applied force or displacement has generally been neglected. In this work we study the adhesive force-displacement response of viral particles against a cell membrane. We have built two models: one in which the viral particle is cylindrical (say, representative of filamentous virus such as Ebola) and another in which it is spherical (such as SARS-CoV-2 and Zika). Our interest is in initial adhesion, in which case deformations are small and the mathematical model for the system can be simplified considerably. The parameters that characterize the process combine into two dimensionless groups that represent normalized membrane bending stiffness and tension. In the limit where bending dominates, for sufficiently large values of normalized bending stiffness, there is no adhesion between viral particles and the cell membrane without applied force. (The zero-external-force contact width and pull-off force are both zero.) For large values of normalized membrane tension, the adhesion between virus and cell membrane is weak but stable. (The contact width at zero external force has a small value.) Our results for pull-off force and zero force contact width help to quantify conditions that could aid the development of therapies based on denying the virus entry into the cell by blocking its initial adhesion.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗

bioRxiv2018

Coarse-Grained Model of the SNARE Complex Shows that Quick Zippering Requires Partial Assembly

Neuronal transmitters are released from nerve terminals via the fusion of synaptic vesicles with the presynaptic membrane. Vesicles become attached to the membrane via the SNARE complex. The SNARE complex comprises the vesicle associate protein Synaptobrevin (Syb), the membrane associated protein syntaxin (Syx), and the cytosolic protein SNAP25, which together form a four-helical bundle. The full assembly of Syb onto the core SNARE bundle promotes vesicle fusion. We investigated SNARE assembly using a coarse-grained model of the SNARE complex. The model retains chemical specificity, and was calibrated using single molecule experiments and all-atom molecular dynamics simulations. Steered force-control simulations of SNARE unzippering by peeling off Syb were used to set up initial disassembled states of the SNARE complex. From these states, the assembly process was simulated. We found that if Syb is in helical form, then the SNARE complex assembles rapidly, on a sub-microsecond time-scale. We found that assembly times grow exponentially with separation distance between Syb and Syx C-termni. The formation of helical turns is likely to substantially decelerate the assembly, consistent with single molecule force experiments that show SNARE assembly duration on the time-scale of hundreds of ms. Since synaptic vesicle fusion occurs at a sub-millisecond time-scale, our results indicate that for biologically relevant rapid assembly the SNARE complex needs to be partially zippered and its constituent helices brought into proximity, possibly by means of molecular chaperones.

biophysics↗