(302e) Structural Analysis of the Gel to Fluid Transition of DSPE Bilayer Using Discontinuous Molecular Dynamics Simulations

Liposomes have been investigated as drug carriers for targeted delivery applications because they are biocompatible and easily release the drugs that they contain in vivo. One way to release drugs in a particular region of the body (e.g. a cancer or tumor) is by heating the affected area up to 43 Cº. The membranes surrounding liposomes within the heated area thus undergo a gel to fluid phase transition in response to heating as the orientation of the carbon tails shifts from trans to gauche. As a consequence, the liposome membrane becomes leaky and the drugs are released. We are using discontinuous molecular dynamics (DMD) simulations combined with the LIME (Lipid Intermediate Resolution Model) force field for lipids to study and design thermally-driven liposomes based on 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine (DSPE). DMD is faster than traditional molecular dynamics simulation since the equations of motion can be solved analytically; this allows us to observe the phase transition of the lipid bilayer over a broad temperature range. We have been able to simulate the spontaneous formation of a DSPE bilayer starting from a random initial configuration at various temperatures (290K ~ 370K). Anaysis of a carbon tail order parameter indicates that the DSPE bilayer exhibits a “gel” phase at low temperature, and a transition to “fluid” phase at 340K. The bilayer thickness is within 3% of the value obtained using atomistic simulation data.