DNA-LIPID COMPLEXES - STABILITY OF HONEYCOMB-LIKE AND SPAGHETTI-LIKE STRUCTURES

A molecular level theory is presented for the thermodynamic stability of two (similar) types of structural complexes formed by (either singl e strand or supercoiled) DNA and cationic liposomes, both involving a monolayer-coated DNA as the central structural unit. In the ''spaghett i'' complex the central unit is surrounded by another, oppositely curv ed, monolayer, thus forming a bilayer mantle. The ''honeycomb'' comple x is a bundle of hexagonally packed DNA-monolayer units. The formation free energy of these complexes, starting from a planar cationic/neutr al lipid bilayer and bare DNA, is expressed as a sum of electrostatic, bending, mixing, and (for the honeycomb) chain frustration contributi ons. The electrostatic free energy is calculated using the Poisson-Bol tzmann equation. The bending energy of the mixed lipid layers is treat ed in the quadratic curvature approximation with composition-dependent bending rigidity and spontaneous curvature. Ideal lipid mixing is ass umed within each lipid monolayer. We found that the most stable monola yer-coated DNA units are formed when the charged/neutral lipid composi tion corresponds (nearly) to charge neutralization; the optimal monola yer radius corresponds to close DNA-monolayer contact. These conclusio ns are also valid for the honeycomb complex, as the chain frustration energy is found to be negligible. Typically, the stabilization energie s for these structures are on the order of 1 k(B)T/Angstrom of DNA len gth, reflecting mainly the balance between the electrostatic and bendi ng energies. The spaghetti complexes are less stable due to the additi onal bending energy of the external monolayer. A thermodynamic analysi s is presented for calculating the equilibrium lipid compositions when the complexes coexist with excess bilayer.