ERI: Revealing the Reconfiguration Dynamics of Lipid Bilayer and Its Hydration Structures with Nanoscale Resolution during Electroporation

South Dakota School Of Mines And Technology, Rapid City SD

Investigators

Abstract

A fundamental question in life science is to understand and control how cell membranes respond to external stimuli. This is important in determining the efficacy of drug delivery. For example, electric fields can create transient pores on a cell membrane, a process called electroporation, which is used to deliver cargo into cells, but it remains a challenge to achieve efficient delivery without causing irreversible damage. This award will use sub-nanometer resolution imaging to capture how cell membranes dynamically respond upon applying an external electric field. The understanding of intracellular delivery gained will not only benefit the biomedical field, but also biomolecule manufacture, gene editing and other intracellular investigations. This imaging capability will also benefit the understanding of solid-liquid interface systems in applications including fuel cells, batteries, and corrosion/erosion processes. In synergy with the research activities, the knowledge of bio-interfaces and imaging techniques will be disseminated to the general public, by developing and using mobile and webpage apps for workflow visualization, doing demos of bio-interfaces to K-12 students and senior residents, and providing training to both undergraduate and graduate students. This award will use an atomic force microscope with sub-nanometer and high temporal resolution to offer the molecular-level imaging, with a focus on revealing the dynamic responses of lipid bilayer and its hydration structure under an external electric field. The understanding of nanoscale interactions involved in the drug delivery process are still limited due to lack of appropriate imaging tools. The key hypothesis in this work is that the hydration structure of lipid bilayer determines the nanoscale interactions of lipid bilayer with drug molecules and the biophysical behavior of lipid bilayer under the external stimuli. Three research thrusts will be initiated: i) imaging the dynamic changes of lipid bilayer under an electric field; ii) capturing the structural changes of hydration structures involved in lipid bilayer reconfiguration; and iii) establishing the structure-property relationship for different types of lipid and solution chemistry. The proposed research activities aim to resolve and understand the pore formation and sealing processes during electroporation of lipid bilayers and reveal the role of hydration structure in this process. The proposed research and education activities will bridge the long-standing knowledge gap in the molecular-level imaging of molecular phenomena at bio-interfaces and offer insights into better engineering of non-viral transfection methods for biomedical purposes. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.