Direct evidence for counterion release upon cationic lipid-DNA condensation

The cooperative condensation of DNA and cationic liposomes to form ordered aggregates in aqueous solution is associated with the release of partially bound counterions. We directly determine the extent of counterion release by separating the supernatant from the precipitated condensates, measuring the conductivity of the solution before and after the phase transition. The extent of counterion release is calculated for a range of lipid/DNA concentration ratios based on the nonlinear Poisson-Boltzmann theory. Both experiment and theory show maximal, essentially complete, release of counterions at the isoelectric point, where the positive (lipid)/negative (DNA) charge ratio is 1:1. Furthermore, at this point the entropic contribution to the condensation free energy is maximal and dominant.