Topological friction strongly affects viral DNA ejection

Abstract

Bacteriophages initiate infection by releasing their double-stranded DNA into the cytosol of their bacterial host. However, what controls and sets the timescales of DNA ejection? Here we provide evidence from stochastic simulations which shows that the topology and organization of DNA packed inside the capsid plays a key role in determining these properties. Even with similar osmotic pressure pushing out the DNA, we find that spatially ordered DNA spools have a much lower effective friction than disordered entangled states. Such spools are only found when the tendency of nearby DNA strands to align locally is accounted for. This topological or conformational friction also depends on DNA knot type in the packing geometry and slows down or arrests the ejection of twist knots and very complex knots. We also find that the family of (2, 2k+1) torus knots unravel gradually by simplifying their topology in a stepwise fashion. Finally, an analysis of DNA trajectories inside the capsid shows that the knots formed throughout the ejection process mirror those found in gel electrophoresis experiments for viral DNA molecules extracted from the capsids.DNA knotting | Monte Carlo simulations B acteriophages are viruses which infect bacteria. They mostly rely on a remarkably simple infection strategy: after landing on the host cell wall, they release their genetic material into its cytoplasm and hijack the cell protein networks to aid capsid formation and phage replication. For double-stranded DNA (dsDNA)-based phages the infection is initiated by the very large pressure (∼10 atm) (1) to which the DNA is subject inside the capsid, where it is packaged to almost crystalline density by a powerful molecular motor (2). Because of the opposing osmotic pressure from the macromolecules in the bacterial cytosol, the later stages of the DNA ejection process in vivo often rely on the host cellular machinery to finalize the viral genome delivery.Although existing theories have stressed the importance of salt-induced interactions and electrostatics on the ejection time (3, 4) these usually underestimate the conformational entropy contribution to the packaging or ejection force by exclusively considering one optimized, ordered DNA arrangement. The impact of highly variable DNA-packing conformations on the ejection process is thus not accounted for a priori.To better understand the impact that DNA spatial arrangement has on its ejection kinetics we consider the ordering effects of local DNA-DNA interactions. We concentrate in particular on the known tendency of contacting dsDNA strands to align at a small angle with respect to each other (regardless of the 3′-5′ orientation in each of the strands). Increasing evidence shows that this cholesteric interaction is not only important for the formation of cholesteric phases in concentrated solutions of DNA (5-8) but can favor the spool-like DNA arrangements of viral DNA (9-11) inside small capsids. Moreover it can control the complexity of DNA self-entanglement in the form of knots (10,(12)(13)(14...

Untying Knotted DNA with Elongational Flows

“…Further, this mechanism clearly extends to all of the (2n + 1) 1 family of torus knots; the addition of additional loops in the knot does nothing to prohibit the coupling of knot rotation and translation. The increased mobility of torus knots appears to be quite general, having been demonstrated in macroscopic shaking chain experiments, 44 simulations of DNA ejection from viral capsids, 45 and simulations of tensioned electrophoresing DNA. 46 We postulate our mechanism plausibly explains these results.…”

Non-monotonous polymer translocation time across corrugated channels: Comparison between Fick-Jacobs approximation and numerical simulations

“…Many biological processes such as viral injection of DNA into host cells [1,2], DNA transport through membrane or organelles [3] and gene transferring between bacteria [4,5] involve the translocation of bio-polymer through nano-channels and nano-pores. Moreover, due to technological applications such as polymer separation, DNA sequencing and protein sensing, polymer translocation phenomena has been largely investigated in recent years [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

Polymer ejection from strong spherical confinement

“…In the bacteriophages the viral DNAs and RNAs are packed to almost crystalline densities [3], realization of which is beyond most computer simulations. Computational investigations of some specific characteristics using closeto-realistic model polymers packed to high densities are typically done using some form of probabilistic Metropolis sampling, see, e.g., [12]. On the other hand investigations using dynamically more realistic molecular dynamics (MD)-based methods typically aim at detailed modeling of a specific polymer and are not very conclusive with regard to general characterization of the polymer ejection.…”