How cells wrap around virus-like particles using extracellular filamentous protein structures

TL;DR

This study uses a computational model to explore how extracellular filamentous structures influence cell wrapping around virus-like particles, revealing optimal conditions for efficient viral uptake and the mechanical factors involved.

Contribution

The paper introduces a novel computational model incorporating filamentous extracellular components to analyze their effect on viral endocytosis.

Findings

Optimal filamentous extracellular component density accelerates viral wrapping.

Cell surface folding around viruses is more efficient than crumple-like wrapping.

Bending rigidity of the cell surface promotes fold formation and force transmission.

Abstract

Nanoparticles, such as viruses, can enter cells via endocytosis. During endocytosis, the cell surface wraps around the nanoparticle to effectively eat it. Prior focus has been on how nanoparticle size and shape impacts endocytosis. However, inspired by the noted presence of extracellular vimentin affecting viral and bacteria uptake, as well as the structure of coronaviruses, we construct a computational model in which both the cell-like construct and the virus-like construct contain filamentous protein structures protruding from their surfaces. We then study the impact of these additional degrees of freedom on viral wrapping. We find that cells with an optimal density of filamentous extracellular components (ECCs) are more likely to be infected as they uptake the virus faster and use relatively less cell surface area per individual virus. At the optimal density, the cell surface folds around the virus, and folds are faster and more efficient at wrapping the virus than crumple-like wrapping. We also find that cell surface bending rigidity helps generate folds, as bending rigidity enhances force transmission across the surface. However, changing other mechanical parameters, such as the stretching stiffness of filamentous ECCs or virus spikes, can drive crumple-like formation of the cell surface. We conclude with the implications of our study on the evolutionary pressures of virus-like particles, with a particular focus on the cellular microenvironment that may include filamentous ECCs.