To model the possible formation of coupled spatial corrugations and charge density modulations in lamellar DNA-lipid complexes, we use a free energy functional which includes the electrostatic, lipid mixing, and elastic degrees of freedom in a self-consistent manner. We find that the balance of forces favors membrane corrugations that are expected to be stable with respect to thermal membrane undulations for a certain range of lipid (charged and uncharged) composition. This may lead to locking between DNA strands in adjacent galleries of the complex. Furthermore, the possibility of membrane corrugations renders the lamellar complex more stable with respect to another, hexagonal, DNA-lipid phase.

We present a theoretical study of the energetics, equilibrium size, and size distribution of membrane pores composed of electrically charged amphipathic peptides. The peptides are modeled as cylinders (mimicking alpha-helices) carrying different amounts of charge, with the charge being uniformly distributed over a hydrophilic face, defined by the angle subtended by polar amino acid residues. The free energy of a pore of a given radius, R, and a given number of peptides, s, is expressed as a sum of the peptides’ electrostatic charging energy (calculated using Poisson-Boltzmann theory), and the lipid-perturbation energy associated with the formation of a membrane rim (which we model as being semitoroidal) in the gap between neighboring peptides. A simple phenomenological model is used to calculate the membrane perturbation energy. The balance between the opposing forces (namely, the radial free energy derivatives) associated with the electrostatic free energy that favors large R, and the membrane perturbation term that favors small R, dictates the equilibrium properties of the pore. Systematic calculations are reported for circular pores composed of various numbers of peptides, carrying different amounts of charge (1-6 elementary, positive charges) and characterized by different polar angles. We find that the optimal R’s, for all (except, possibly, very weakly) charged peptides conform to the ‘‘toroidal’’ pore model, whereby a membrane rim larger than similar to1 nm intervenes between neighboring peptides. Only weakly charged peptides are likely to form ‘‘barrel-stave’’ pores where the peptides essentially touch one another. Treating pore formation as a two-dimensional self-assembly phenomenon, a simple statistical thermodynamic model is formulated and used to calculate pore size distributions. We find that the average pore size and size polydispersity increase with peptide charge and with the amphipathic polar angle. We also argue that the transition of peptides from the adsorbed to the inserted (membrane pore) state is cooperative and thus occurs rather abruptly upon a change in ambient conditions.

In a previous communication (Kindt et al., 2001) we reported preliminary results of Brownian dynamics simulation and analytical theory which address the packaging and ejection forces involving DNA in bacteriophage capsids. In the present work we provide a systematic formulation of the underlying theory, featuring the energetic and structural aspects of the strongly confined DNA. The free energy of the DNA chain is expressed as a sum of contributions from its encapsidated and released portions, each expressed as a sum of bending and interstrand energies but subjected to different boundary conditions. The equilibrium structure and energy of the capsid-confined and free chain portions are determined, for each ejected length, by variational minimization of the free energy with respect to their shape profiles and interaxial spacings. Numerical results are derived for a model system mimicking the lambda-phage. We find that the fully encapsidated genome is highly compressed and strongly bent, forming a spool-like condensate, storing enormous elastic energy. The elastic stress is rapidly released during the first stage of DNA injection, indicating the large force (tens of pico Newtons) needed to complete the (inverse) loading process. The second injection stage sets in when similar to1/3 of the genome has been released, and the interaxial distance has nearly reached its equilibrium value (corresponding to that of a relaxed torus in solution); concomitantly the encapsidated genome begins a gradual morphological transformation from a spool to a torus. We also calculate the loading force, the average pressure on the capsid’s walls, and the anisotropic pressure profile within the capsid. The results are interpreted in terms of the (competing) bending and interaction components of the packing energy, and are shown to be in good agreement with available experimental data.

Osmotic shock is a familiar means for rupturing viral capsids and exposing their genomes intact. The necessary conditions for providing this shock involve incubation in high-concentration salt solutions, and lower permeability of the capsids to salt ions than to water molecules. We discuss here how values of the capsid strength can be inferred from calculations of the osmotic pressure differences associated with measured values of the critical concentration of incubation solution.

The adsorption of charge rigid macromolecules, such as proteins from solution, on mixed (charged and neutral) lipid membranes is affected by several important factors. First, the mobile lipids in the membrane may rearrange, and demix locally to match the charge density of the apposed macromolecule, thus lowering the adsorption free energy. On the other hand, the (electrostatic) interaction between adsorbed macromolecules tends to lower the saturation coverage of the membrane. Additional factors, such as non-ideal lipid demixing or an elastic membrane response, enhanced by the presence of the charged macromolecules, may be at the base of the experimentally observed formation of high density protein domains and lateral macro-phase separation in lipid membranes. (C) 2002 Elsevier Science B.V. All rights reserved.

Macroion adsorption on a mixed, fluid, lipid membrane containing oppositely charged lipids induces local changes in lipid composition at the interaction zones, and gradients at their boundaries. Including these effects in the free energy of the macroion-dressed membrane we derive its spinodal equation, and show that nonideal lipid mixing can lead to (lipid-mediated) attraction between macroions and lateral phase separation in the composite membrane. The critical nonideality for this transition is substantially smaller than that of the bare lipid membrane, decreasing with macroion size and charge. That is, the lipid membrane is destabilized by macroion adsorption.

We calculate the forces required to package (or, equivalently, acting to eject) DNA into (from) a bacteriophage capsid, as a function of the loaded (ejected) length, under conditions for which the DNA is either self-repelling or self-attracting. Through computer simulation and analytical theory, we find the loading force to increase more than 10-fold (to tens of piconewtons) during the final third of the loading process; correspondingly, the internal pressure drops 10-fold to a few atmospheres (matching the osmotic pressure in the cell) upon ejection of just a small fraction of the phage genome. We also determine an evolution of the arrangement of packaged DNA from toroidal to spool-like structures.