MULTISCALE, MULTIPHYSICS STUDY OF THERMAL AND NONTHERMAL DIRECTED ENERGY BIOLOGICAL EFFECTS
Abstract
MULTISCALE, MULTIPHYSICS STUDY OF THERMAL AND NONTHERMALDIRECTED ENERGY BIOLOGICAL EFFECTSProgram Officer: Tim Bentley, ONR Code 342Although electromagnetic radiation in both wideband (electric pulses (EPs) from picosecond to millisecond duration) and narrowband (Hz to THz) have widespread clinical and defense applications, including wound healing, microorganism inactivation, platelet activation, and nonlethal defense, much remains incompletely characterized concerning the combination of thermal and nonthermal biological effects. EPs with durations longer than the membrane charging time ( a few hundred nanoseconds) typically permeabilize the membrane through electroporation. Recent studies have explored the impact of thermal effects on EP application for irreversible electrochemotherapy effectiveness and molecular dynamics (MD) simulations have shown that a slight temperature change can increase membrane permeabilization. Although EPs are typically considered athermal, a slight (~1 K), theory and finite element models (FEM) show that a rapid rise (~ns) in temperature for short duration EPs or high frequency RF (radiofrequency) fields can induce a large temperature gradient across the cell membrane. MD simulations showed that the temperature gradient can then facilitate membrane permeabilization. Experimentally, reproducing experimstent thermal and nonthermal biological effects from the organism to the cell.Thus, while several recent studies have explored the combination of thermal and nonthermal effects at various scales, translating between exposure modality and mechanism remains poorly understand and simultaneously translating biological effects from the subcellular level to the cellular level remains incomplete. A multiscale and multiphysics characterization of electrical bioeffects is crucial for both developing a predictive capability to guide experimental design and provide a fundamental understanding of already observed biological phenomena. A clear link between simulation, theory, and experiment is crucial for a comprehensive study characterizing these biophysical phenomena. This is particularly critical when discerning the implications of potential thermal and nonthermal effects of applied pulsed RF from source to the molecular level.This proposal is part of two linked proposals sent to the Army Research Office (ARO) and the Office of Naval Research (ONR). The ARO portion will fund experimental studies into the impact of cellular dielectric properties as a function of temperature, wh RF source, this effort will also explore fundamental biological and genomic effects of pulsed RF effects to compare to the theory. The ARO effort will also assess the temperature gradients under various RF waveforms for feeding into mathematical models for membrane pore formation and molecular dynamics simulations. The ONR effort will focus on developing a full-body FEM for translating the RF source to electromagnetic fields inside the body. These will be coupled to a simplified model for membrane permeabilization using an RF field for non-excitable and excitable cells that will be developed under the ARO effort. Texas Tech University (TTU) will develop a full Smoluchowski equation (SME) for membrane pore formation under pulsed RF fields that includes temperature, temperature gradients, and nonspherical cells as part of the ONR effort. TTU will also perform MD simulations of non-excitable and excitable cells to explore the impact of RF fields at the lipid bilayer layer and then iterate between them and the SME.This proposal requests $542,720 with a period of performance from 01OCT2020 to 30SEP2023.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 15, 2021
- Source ID
- N000142112055
Entities
People
- Allen L Garner
Organizations
- Office of Naval Research
- Purdue University
- United States Navy