Dynamics of polymer ejection from capsid

Abstract

Polymer ejection from a capsid through a nanoscale pore is an important biological process with relevance to modern biotechnology. Here, we study generic capsid ejection using Langevin dynamics. We show that even when the ejection takes place within the drift-dominated region there is a very high probability for the ejection process not to be completed. Introducing a small aligning force at the pore entrance enhances ejection dramatically. Such a pore asymmetry is a candidate for a mechanism by which viral ejection is completed. By detailed high-resolution simulations we show that such capsid ejection is an out-of-equilibrium process that shares many common features with the much studied driven polymer translocation through a pore in a wall or a membrane. We find that the ejection times scale with polymer length, τ ∼ N α . We show that for the pore without the asymmetry the previous predictions corroborated by Monte Carlo simulations do not hold. For the pore with the asymmetry the scaling exponent varies with the initial monomer density (monomers per capsid volume) ρ inside the capsid. For very low densities ρ 0.002 the polymer is only weakly confined by the capsid, and we measure α = 1.33, which is close to α = 1.4 obtained for polymer translocation. At intermediate densities the scaling exponents α = 1.25 and 1.21 for ρ = 0.01 and 0.02, respectively. These scalings are in accord with a crude derivation for the lower limit α = 1.2. For the asymmetrical pore precise scaling breaks down, when the density exceeds the value for complete confinement by the capsid, ρ 0.25. The high-resolution data show that the capsid ejection for both pores, analogously to polymer translocation, can be characterized as a multiplicative stochastic process that is dominated by small-scale transitions.

Polymer ejection from strong spherical confinement

“…Also the viscosity in their experiments is much larger than in our simulations. with previous findings [1][2][3][4][6][7][8][9], scaling τ ∼ N β 0 is obtained. Here, β = 1.362 ± 0.05, 1.325 ± 0.04, 1.293 ± 0.04, 1.299 ± 0.03, and 1.300 ± 0.04 for ρ 0 = 0.5, 0.75, 1, 1.25, and 1.5, respectively.…”

“…An important class of such processes is the capsid ejection where a polymer is initially in a compact conformation inside a capsid and then ejects outside through a pore a few nanometers wide. By far the most important biological process of this class is the viral packaging in and ejection from bacteriophages [1][2][3][4][5][6][7][8][9]. The ejection of double-stranded (ds) DNA is clearly the most studied case.…”

Uniform description of polymer ejection dynamics from capsid with and without hydrodynamics

“…Packaging and ejection of macromolecules in confinements are of high interest due to the potential technological and medical applications, such as drug delivery and gene therapy [1]. The basic understanding of these processes is important also due to the relevant fundamental biological processes, the most prominent of which is the viral packaging in and ejection from bacteriophages [2][3][4][5][6][7][8][9][10]. The theoretical treatments of polymer ejection are strictly based on fully flexible chains [2,8,9], in spite of the experimental studies being almost solely done on semiflexible double-stranded DNA.…”

Scaling Behaviors of a Polymer Ejected from a Cavity through a Small Pore

“…The ejection time was deduced to scale asymptotically asat the osmotic driven stage. Simulations, on the other hand, revealed that translocation behaviors can be altered by the details of the escape pore [16,17], the cavity [18,19], the solvent [20,21], the chain stiffness [19,22], etc. Despite of the varieties, universalities can be still traced.…”