Role of Charge Regulation and Size Polydispersity in Nanoparticle Encapsulation by Viral Coat Proteins

Abstract

Nanoparticles can be encapsulated by virus coat proteins if their surfaces are functionalized to acquire a sufficiently large negative charge. A minimal surface charge is required to overcome (i) repulsive interactions between the positively charged RNA-binding domains on the proteins and (ii) the loss of mixing and translational entropy of RNA and capsid coat proteins. Here, we present a model describing the encapsulation of spherical particles bearing weakly acidic surface groups and investigate how charge regulation and size polydispersity impact upon the encapsulation efficiency of gold nanoparticles by model coat proteins. We show that the surface charge density of these particles cannot be assumed fixed, but that it adjusts itself to minimize electrostatic repulsion between the charges on them and maximize the attractive interaction with the RNA binding domains on the proteins. Charge regulation in combination with the natural variation of particle radii has a large effect on the encapsulation efficiency: it makes it much more gradual despite its inherently cooperative nature. Our calculations rationalize recent experimental observations on the coassembly of gold nanoparticles by brome mosaic virus coat proteins.

Effects of RNA branching on the electrostatic stabilization of viruses

“…Variation of the free energy yields the same Euler-Lagrange equations as given in Eqs. (6), (7), (8) subject to the constraint, Eq. (4).…”

“…In the prevailing paradigm this assembly is predominantly driven by generic, nucleotide sequence independent, electrostatic interactions [2] between the negative charges on the RNA phosphate backbone and the positive charges on the virus capsid proteins (CP) [3][4][5][6][7][8]. Recent experiments have indeed abundantly verified the importance of the "chargematching hypothesis", based on the preponderance of electrostatic interactions between the capsid proteins and the RNA for proper genome packaging [9].…”

Feasibility of Cowpea chlorotic mottle virus-like particles as scaffold for epitope presentations

“…CCMV particles have already been shown feasible for applications in biotechnology such as the encapsulation of anionic non-genomic polymers in CCMV VLPs lacking genomic materials [ 31 ]. Recently also DNA origami structures coated with CCMV capsid proteins were efficiently delivered into human cells [ 32 ], and viral coat proteins shown to encapsulate gold nanoparticles [ 33 ].…”

Effects of long-range interactions on curvature energies of viral shells

“…The variation of the charge ratio r can be seen as a proxy for the pH dependence of both surface charge densities in a more complete theory of virus shell electrostatic, that would consistently include also charge regulation of the capsid proteins [19,47,48]. Charge regulation refers to the details of the protonation/deprotonation equilibria at the dissociable sites of the capsid proteins amino acids as formalized in the seminal work of Ninham and Parsegian [49] and formulated within the Poisson-Boltzmann (PB) theory of electrostatic interactions [7].…”