Percolation Theory Reveals Biophysical Properties of Virus-like Particles

Abstract

The viral protein containers that encapsulate a virus’ genetic material are repurposed as virus-like particles in a host of nanotechnology applications, including cargo delivery, storage, catalysis, and vaccination. These viral architectures have evolved to sit on the knife’s edge between stability, to provide adequate protection for their genetic cargoes, and instability, to enable their efficient and timely release in the host cell environment upon environmental cues. By introducing a percolation theory for viral capsids, we demonstrate that the geometric characteristics of a viral capsid in terms of its subunit layout and intersubunit interaction network are key for its disassembly behavior. A comparative analysis of all alternative homogeneously tiled capsid structures of the same stoichiometry identifies evolutionary drivers favoring specific viral geometries in nature and offers a guide for virus-like particle design in nanotechnology.

Engineering Metastability into a Virus-like Particle to Enable Triggered Dissociation

“…This observation is consistent with percolation theory, , which posits that when a lattice incorporates enough flaws, it will catastrophically collapse. Percolation theory has been applied to HBV and generalized to other icosahedral symmetries. , Finally, at low βME concentrations and low ionic strength, we observe the appearance of small oligomers of dimers (Figure C). We suspect that these small oligomers transiently accumulate because they are not forced into a capsid-like conformation, and thus, there is little driving force for their dissociation.…”

“…This model may be general to other disassembly reactions and, indeed, may serve as part of the basis for HBV capsid’s hysteresis to dissociation. , We also observe the appearance of intermediates between T = 4 capsid and 90-mer. This observation is consistent with percolation theory, , which posits that when a lattice incorporates enough flaws, it will catastrophically collapse. Percolation theory has been applied to HBV and generalized to other icosahedral symmetries. , Finally, at low βME concentrations and low ionic strength, we observe the appearance of small oligomers of dimers (Figure C).…”

“…24,75 We also observe the appearance of intermediates between T = 4 capsid and 90-mer. This observation is consistent with percolation theory, 57,58 which posits that when a lattice incorporates enough flaws, it will catastrophically collapse. Percolation theory has been applied to HBV and generalized to other icosahedral symmetries.…”

“…The persistence of 90-mers may indicate that T = 3 particles are more resistant to dissociation in high ionic strength or that 90-dimer intermediates transiently accumulate. This last possibility is consistent with capsid dissociation passing through a percolation threshold where HBV capsids can persist till about 25% of their subunits are removed, after which they catastrophically fail. ,− …”

Exosomes-based particles as inhalable COVID-19 vaccines

“…Besides, several vaccines need to be stored in deep freezing condition to keep efficacy of bioactive, which has brought great cost and difficulties in long-term storage and transportation. Virus-like particles (VLPs), usually an artificial nanostructure, own similar morphology to natural virus yet fail to reproduce the virus and infect host [ [17] , [18] , [19] ], which could trigger robust cellular or humoral immunity reaction to against virus invasion [ 20 , 21 ]. Particularly, exosomes are a class of naturally-derived extracellular vesicles (approximately 100 ​nm in diameter) secreted from most cells, which have raised remarkable attention in drug delivery and immunization area [ 16 ] ( Fig.…”