Esin B. Sözer
Research Assistant Professor
Old Dominion University
Frank Reidy Research Center for Bioelectrics
Laboratory of Multiscale Bioelectrical Interactions
Our project "Breaching the cell membrane with electric fields—connecting nanoscale computational physics to cellular experiments" with PI: Esin B. Sözer and co-PI: Willy Wriggers (http://biomachina.org/) got awarded a ODU Multidisciplinary Biomedical Research Seed Funding for the year 2020!
We are excited to start our project together with our new team member Biomedical Engineering Ph.D. student Anthony Owusu-Mensah.
Selected Research Projects
Breaching the cell membrane with electric fields—connecting nanoscale computational physics to cellular experiments: The membrane consists of amphiphilic phospholipid molecules (polar phosphate heads and fatty lipid tails) that in water-based solvent self-organize into a stable lipid bilayer by a process known as the hydrophobic effect. For any transport to occur, the normally stable membrane bilayer must be temporarily disrupted. One of my expertise is in microscopic imaging of molecular transport into mammalian cells after brief pulsed electric field exposures (see https://www.sozerlab.com/research-home/publications). I develop my own image processing tools for analysis of imaging experiments. You can find these codes on this website (www.sozerlab.com/research-home/image-processing-scripts). The traditional view of electroporative transport theory involves formation of conductive hydrophilic lipid pores on the membrane, when the energy required to disrupt the membrane is lowered by the external electric field. This theoretical framework largely ignores the nonzero membrane potentials after electric pulse exposure, thus assumes a solely diffusive transport. Recently we showed experimentally that the electroporative transport even after a brief (6 ns) perturbation is not solely diffusive and is modified significantly by a nonzero global membrane potential (Sözer et al. BMC Biophysics, 2018).
The local nanoscale membrane potential can further affect the transport by lowering the energy barrier for reorganization of membrane and formation of pores. This key local mechanism can not be observed experimentally. Instead, it requires atomistic molecular dynamics (MD) simulations and their careful statistical analysis. Our project with lead PI: Esin B. Sözer and co-PI: Willy Wriggers (http://biomachina.org/) has recently got awarded a ODU Multidisciplinary Biomedical Research Seed Funding for the year 2020. We will combine two distinct computational methods to investigate the effect of local potential on transport through simulated lipid electropore systems: one based on electromagnetic theory, one on complex statistical analysis and then compare the results to experimental measurements of global events with cells.
Modulation of biological responses to fast electric pulses : As a part of AFOSR MURI project named "Nanoelectropulse-Induced Electromechanical Signaling and Control of Biological Systems " with lead PI Dr. Andrei Pakhomov of ODU FRRCBE, I work with Dr. Tom Vernier (http://www.bioelectrophysics.org) to study modulation of biological responses to electric fields by field reversal ( nanosecond bipolar cancellation). Under this umbrella, I lead two lines of projects, one in molecular transport measurements of U-937 cells; and the other in electrostimulation measurements by Ca2+ imaging of adrenal chromaffin cells using 2 ns electric pulses. Electrostimulation project is in close collaboration with Dr. Josette El Zaklit (https://www.unr.edu/ebme/people/elzaklit) and Dr. Gale Craviso (https://www.unr.edu/molecular-biosciences/faculty/gale-craviso) at the University of Nevada Reno.
Electrical stress on GUVs: We study effect of very short (few nanoseconds) electrical stress on pure lipid vesicles in collaboration with Dr. Sourav Haldar (https://scholar.google.com/citations?user=EyBW4YIAAAAJ&hl=en), and Dr. Joshua Zimmerberg's laboratory at NIH, NICHD (https://irp.nih.gov/pi/joshua-zimmerberg). GUVs serve as a simple model to understand the interactions at the lipid level as opposed to complex live cell membranes. We connect our experimental results to molecular dynamics simulations we run at ODU.
Molecular dynamics (MD) simulations of lipid electropores: I develop tools to analyze MD simulation trajectories of electropores. Examples include scripts for centering of an electropore in the simulation box, measuring the pore radius, pore lifetime, transport through a pore, and headgroup dipole angle. You can find the relevant codes on this website (under "MD Scripts": www.sozerlab.com/research-home/md-scripts). Federica Castellani and Tom Vernier lead these MD simulation efforts (www.bioelectrophysics.org).
Neurostimulation and neuromodulation of C. elegans: The nematode Caenorhabditis elegans (C. elegans) is a well-studied model organism, the first animal with completely traced embryonic and post-embryonic cell lineages, a cell-by-cell reconstruction of the complete nervous system, and the first animal whose genome was sequenced. C. elegans is a very suitable candidate for full organism investigations that are especially important for therapeutic applications. I am interested in studies of behavior modification due to specific biological pathways that can be affected by electric stimulus. Such effects can modify the behavior of worms, especially combined with environmental and genetic factors.
Bioelectrically-stimulated epigenetic modifications: I am interested in triggering beneficial epigenetic modifications such as reactivation of tumor suppressor genes in cancer via bioelectrical stimulation. Bioelectrical signals can modulate intracellular calcium in cells, which regulate many biological processes including epigenetics. I hope to fine-tune electrical parameters of bioelectrical stimulation for optimal therapeutic effect of epigenetic pathways. I am in the process of gathering preliminary data together with my collaborator Dr. Barbara Benassi of ENEA (http://www.enea.it/en), Rome, Italy.
J. Zaklit, P.T. Vernier, G. L. Craviso, E. B. Sözer, “Electrostimulation bovine chromaffin cells and cancellation of it with 2 ns electric pulses”, in preparation.