Mesoscale transport of enveloped viruses

Abstract

Enveloped viruses are characterized by spike proteins that protrude from and decorate the viral membrane. These proteins play a crucial role in host cell interactions and exhibit dynamic behaviors, such as tilting, lateral diffusion, and clustering, which vary across different types of enveloped viruses. For instance, SARS-CoV-2 spikes tilt to facilitate receptor binding, influenza spikes migrate during infection, and HIV (Human Immunodeficiency Virus) spikes migrate and cluster to enhance infectivity. In this study, we investigate how such dynamics influence the virus mobility. We characterize viral mobility through translational and rotational diffusion coefficients using a mesoscopic model that incorporates the dynamics of both the flexible spike proteins and the viral envelope. Using the smoothed dissipative particle dynamics method, we construct three virion models with varying spike flexibility. The first is a fully rigid virus with static spikes, the second is a model with spikes that tilt but remain fixed in position, and the third is a model allowing both tilting and lateral diffusion of spikes across the envelope. Our results show that spike flexibility primarily affects rotational diffusion, whereas the envelope dominates the translational mobility of the virus. We also explore spike clustering driven purely by hydrodynamic interactions and compare with an experimental model reference using DNA-PAINT super-resolution imaging of HIV-like particles. We identify that hydrodynamic interactions alone can be responsible for the dynamic clustering of spike proteins where the characteristic size and lifespan of such clusters indicate predominantly doublet and triplet formations. Our findings highlight the role of spike dynamics in whole virion mobility and motivate further investigations with time-resolved experimental evidence to fully characterize clustering behavior.