The formation and closure of aqueous pores in lipid bilayers is a key step in various biophysical processes. Large pores are well described by classical nucleation theory, but the free-energy landscape of small, biologically relevant pores has remained largely unexplored. The existence of small and metastable "prepores" was hypothesized decades ago from electroporation experiments, but resolving metastable prepores from theoretical models remained challenging. Using two complementary methods-atomistic simulations and self-consistent field theory of a minimal lipid model-we determine the parameters for which metastable prepores occur in lipid membranes. Both methods consistently suggest that pore metastability depends on the relative volume ratio between the lipid head group and lipid tails: lipids with a larger head-group volume fraction (or shorter saturated tails) form metastable prepores, whereas lipids with a smaller head-group volume fraction (or longer unsaturated tails) form unstable prepores.

We combine dynamic self-consistent field theory with the string method to calculate the minimum energy path to membrane pore formation and rupture. In the regime where nucleation can occur on experimentally relevant time scales, the structure of the critical nucleus is between a solvophilic stalk and a locally thinned membrane. Classical nucleation theory fails to capture these molecular details and significantly overestimates the free energy barrier. Our results suggest that thermally nucleated rupture may be an important factor for the low rupture strains observed in lipid membranes.

We perform molecular dynamics simulations on a set of ionomer melts in the presence of a static, external electric field. We employ the same coarse-grained bead–spring model from our previous simulations, which characterized the zero-field morphologies and dynamics of the isolated or percolated ionic aggregates observed in these systems. Here we investigate the electric field effects on these aggregates. In the linear response regime, the morphology of both isolated and percolated aggregates is unaltered because the force between the two ions at contact is much stronger than the force on an ion due to the external field. However, the same fields are strong enough to bias the local ion dynamics so that ions in the percolated systems, which contain a continuous ionic network, transition to the steady state drift regime. Furthermore, the field biases the motion of oppositely charged ions in opposite directions and decorrelates the ionic aggregates along the field direction. In the systems with isolated ionic aggregates, higher fields are required to observe the same dynamical response. Finally, we find that the conductivity is strongly influenced by the equilibrium aggregate morphologies of these systems; the ionomers with percolating ionic aggregates have the largest conductivities.

We establish an appropriate thermodynamic framework for determining the optimal genome length in electrostatically driven viral encapsidation. Importantly, our analysis includes the electrostatic potential due to the Donnan equilibrium, which arises from the semipermeable nature of the viral capsid, i.e., permeable to small mobile ions but impermeable to charged macromolecules. Because most macromolecules in the cellular milieu are negatively charged, the Donnan potential provides an additional driving force for genome encapsidation. In contrast to previous theoretical studies, we find that the optimal genome length is the result of combined effects from the electrostatic interactions of all charged species, the excluded volume and, to a very significant degree, the Donnan potential. In particular, the Donnan potential is essential for obtaining negatively overcharged viruses. The prevalence of overcharged viruses in nature may suggest an evolutionary preference for viruses to increase the amount of genome packaged by utilizing the Donnan potential (through increases in the capsid radius), rather than high charges on the capsid, so that structural stability of the capsid is maintained.polyelectrolyte | viral assembly T he most prevalent viruses in nature are single-stranded RNA viruses with the genetic material enclosed in icosahedral-shaped capsids made up of 60 T protein units, where the T-number is a small integer index. The protein units (capsomers) often contain highly basic peptide arms that extend into the capsid interior and, under physiological conditions, are positively charged. Electrostatic attraction provides the driving force for encapsidating the negatively charged RNA, which, in turn, helps overcome the electrostatic repulsion among the capsomers during the capsid assembly.In a series of classic experiments, Bancroft and coworkers (1, 2) demonstrated that certain viruses can encapsidate nonnative RNA and even generic polyanions. Dominance of the electrostatics as the driving force for viral assembly has led to the expectation of a simple relationship between the total capsid charge Q P and the genome charge Q R , as every nucleotide carries one unit of negative charge. Belyi and Muthukumar (3) compiled data for 19 wild type viruses from several viral families and found an apparent "universal" charge ratio of Q R ∕Q P ≈ 1.6, which they explained by combining the ground-state dominance approximation for polyelectrolyte binding to an oppositely charged polymer brush with the Manning condensation theory (4). The former predicts a 1∶1 charge ratio and the latter is used as a qualitative argument for the actual charge on the RNA being less than the nominal charge. Hu, et al. (5), however, assumed that the RNA winds around individual peptide arms and found that the viruses are most stable when the total contour length of the RNA is close to the total length of the peptide arms; this roughly gives a charge ratio of 2. In other works that ignore the peptide arms completely, there is additional disagreemen...