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Molecular Dynamics Simulations of Asymmetric Phospholipid Bilayers with Supra-Physiological Transmembrane Potentials

Matthew J. Ziegler, Mork Family Department of Chemical Engineering and Materials Science, University of Southern California Viterbi School of Engineering: MOSIS, Information Sciences Institute, 4676 Admiralty Way, Marina Del Rey, CA 90230 and P. Thomas Vernier, Electrical Engineering, University of Southern California Viterbi School of Engineering: MOSIS, Information Sciences Institute, 4676 Admiralty Way, Marina Del Rey, CA 90292.

 

Electroporation technology is widely used to transport normally excluded substances into biological cells through conductive pores in the cell membrane.  With appropriate values for field amplitude and pulse duration, electroporated cells recover. Pulses that are too long or fields that are too high (excessive total energy) cause irreversible membrane damage and cell death.  

Nanosecond, megavolt-per-meter pulses (high fields but low total energy) porate cells in a non-conventional manner that is not well understood.  Pore formation, initiated by water intruding into the low-dielectric interior of the lipid bilayer at the cathode-facing side of the membrane, can occur in less than one nanosecond depending on the applied field. Hydrophobic pores, highly ordered columns of water molecules spanning the membrane, decay within a few nanoseconds when the electric field is removed.  When the field is sufficiently high, hydrophobic pores expand and become lined by lipid headgroups, a process driven primarily by entropic considerations.  Ions and charged lipids such as phosphatidylserine (PS) migrate electrophoretically through the aqueous column and along the pore wall respectively — ions typically as hydrated charges and PS with its head group solvated at the water interface and its hydrocarbon tail embedded in the membrane.

The aims of this study are to: 1) characterize and classify lipid bilayer pores according to the water dipole orientation and pore diameter; 2) monitor the transport rates of charged species within the pores; 3) describe the thermodynamics associated with transmembrane transport; 4) evaluate proposed mechanisms for experimentally observed phosphatidylserine translocation in megavolt-per-meter fields.