Microsecond Kinetics of Ion Transport and Membrane Interface Binding Before, During, and After Lipid Electropore Formation
Batten College of Engineering & Technology
Ph.D. Engineering - Biomedical Engineering
Molecular dynamics simulations of lipid membranes reveal the nanoscale evolution of biophysical systems, including complex processes that are not observable with conventional experimental methods. Among these processes, electroporation, also called electropermeabilization, is used in medicine and biology to introduce drugs, nucleic acids, and other normally impermeant material into cells. It is known that the application of strong transmembrane electric fields causes the formation of bilayer-spanning water bridges and conductive lipid pores, and that material otherwise not able to go through the cell membrane can enter or exit the cell through these breaches of the membrane barrier. Knowledge about how specific ions and molecules are transported through electropermeabilized membranes, however, is very limited. Our simulations focus on the dynamics of ion-membrane interactions during electroporation. We describe the previously unexplored microsecond kinetics of ion binding to phospholipid bilayers and transport through lipid electropores in double bilayer systems containing K+, Ca2+, and Cl-. A double bilayer system allows us to simulate the different ion concentrations inside and outside the cell and to study their dynamics before, during and after the pulse. In particular, the intracellular distribution of Ca2+ is a key component in the operation of numerous regulatory and signaling pathways. Little is known about the evolution of the threedimensional [Ca2+] profile during the nanoseconds and microseconds after a porating electric pulse. Does Ca2+ diffuse freely into the cytoplasmor is it bound quickly to the intracellular interface of the lipid bilayer? Molecular simulations allow us to explore this nanoscale world in search of answers to these questions.
Castellani, Federica; Sözer, Esin B.; and Vernier, P. Thomas, "Microsecond Kinetics of Ion Transport and Membrane Interface Binding Before, During, and After Lipid Electropore Formation" (2019). College of Engineering & Technology (Batten) Posters. 8.