Computer simulation of DNA interacting electrostatically with phosphatidylcholine and trimethylammoniumpropane interfaces

The region of a lipid membrane, with all hydrocarbon chains equal, embedded in an aqueous solution and interacting with a single DNA molecule, has been modelled. The lattice model used assigned an area characteristic of a lipid molecule in a gel phase to each lattice site. In a fluid phase two lipid molecules occupy three sites. We studied a membrane composed of lipids with phosphatidylcholine (PC) and trimethylammoniumpropane (TAP) headgroups. Lipid headgroup states were enumerated as described elsewhere (Pink et al., Biochim. Biophys. Acta, 1988, 1368, 289). Here charged lipid moieties were represented by point charges inside an excluded volume. The aqueous solution was modelled as a linearized Poisson–Boltzmann system characterized by a Debye screening length, κ−1. We employed standard Monte Carlo computer simulation techniques. We came to the following conclusions. (a) In the absence of DNA, PC and TAP headgroup pairs formed dynamic bound states in a gel phase. These did not occur if the PC was represented as an object carrying no charges. Accordingly, although PC carries zero net charge, it is important to represent the charged moieties explicitly. The gel–fluid phase transition in a 1:1 PC–TAP membrane (with equal hydrocarbon chain lengths) might thus involve not only hydrocarbon chain disordering but also the break-up of the dynamical PC–TAP bound pairs. (b) Increasing TAP concentration resulted in changing the orientation of the PC dipole. (c) DNA binding is a complex process and can involve weak binding even to a pure PC interface (which could, however, be disrupted by membrane undulations not modelled here) and tighter binding when TAP is present. The minimum concentration for the latter depends upon κ. DNA binding at low TAP concentrations would be changed if the PC was represented by a chargeless object. (d) A bound DNA changes the headgroup orientation in its proximity and also results in increased headgroup lateral packing in the immediate neighbourhood of the DNA. The latter could result in denser lateral hydrocarbon chain packing in the neighbourhood of the DNA. Both of these phenomena exhibited a dependence upon the TAP concentration. (e) The average lipid–DNA binding energies per DNA PO2− group can be as large as 2kBT or more depending upon the TAP concentration. (f ) DNA can be unbound by changing the ionic concentration. We compare our results with experimental data and other simulations.

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