Free Energy Cost of Interdigitation of Lamellar Bilayers of Fatty Alcohols with Cationic Surfactants from Molecular Dynamics Simulations.

Cationic surfactant mixed with fatty alcohol as cosurfactant in excess water can form stable emulsions, known as "lamellar gel networks," that contain extended and interconnected networks of swollen bilayers, including ones with in-plane liquidlike disorder (Lα phase) and solidlike order (Lβ phase). To study their structure and thermodynamics, molecular dynamics (MD) simulations with lateral pressure and temperature scans along reversible pathways were used to drive reversible phase changes, including formation at negative lateral pressure of the LβI phase with interdigitated tails of opposing leaflets. Thermodynamic integration, with extrapolations to infinitely slow scans, yielded a free energy difference between the interdigitated LβI and non-interdigitated Lβ phases of 2.4 ± 0.5 kJ/mol, which is consistent with the spontaneous formation of the Lβ phase under atmospheric pressure in simulation. Thermodynamic cycles involving temperature and lateral pressure for which the free energy difference is identically zero were constructed as negative controls to verify the method. Using lateral pressure, including negative lateral pressure, helps avoid kinetic bottlenecks that occur when temperature alone is used as the control variable. The method, using negative lateral pressure, should be widely applicable to other bilayers to identify molecular properties that control interdigitation and other bilayer properties.