STRUCTURE, STABILITY, AND THERMODYNAMICS OF LAMELLAR DNA-LIPID COMPLEXES

We develop a statistical thermodynamic model for the phase evolution o f DNA-cationic lipid complexes in aqueous solution, as a function of t he ratios of charged to neutral lipid and charged lipid to DNA. The co mplexes consist of parallel strands of DNA intercalated in the water l ayers of lamellar stacks of mixed lipid bilayers, as determined by rec ent synchrotron x-ray measurements Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA-induced spatial inhomogenei ties in the bilayer charge densities are included. The relevant nonlin ear Poisson-Boltzmann equation is solved numerically, including self-c onsistent treatment of the boundary conditions at the polarized membra ne surfaces. For a wide range of lipid compositions, the phase evoluti on is characterized by three regions of lipid to DNA charge ratio, rho : 1) for low rho, the complexes coexist with excess DNA, and the DNA-D NA spacing in the complex, d, is constant; 2) for intermediate rho, in cluding the isoelectric point rho = 1, all of the lipid and DNA in sol ution is incorporated into the complex, whose inter-DNA distance d inc reases linearly with rho; and 3) for high rho, the complexes coexist w ith excess liposomes (whose lipid composition is different from that i n the complex), and their spacing d is nearly, but not completely, ind ependent of rho. These results can be understood in terms of a simple charging model that reflects the competition between counterion entrop y and inter-DNA (rho < 1) and interbilayer (rho > 1) repulsions. Final ly, our approach and conclusions are compared with theoretical work by others, and with relevant experiments.