Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Poster Abstracts

33-POS Board 9 STRAIN RESPONSE OF A SIMULATED LIPID BILAYER TO OSCILLATING PRESSURE IN THE MHZ RANGE Kyrstyn S. Ong 1 ; Merritt Maduke 2 ; Evan Reed 1 ; Stephen Baccus 3 ; 1 Stanford University, Department of Materials Science and Engineering, Stanford, CA, USA 2 Stanford University, Department of Molecular and Cellular Physiology, Stanford, CA, USA 3 Stanford University, Department of Neurobiology, Stanford, CA, USA Ultrasound has been shown in many species to modulate neural activity by either exciting or inhibiting neurons, but ultrasonic effects at the molecular level are unclear 1 . Because ultrasound delivers acoustic energy in the form of a pressure wave, it may act in part through a mechanical mechanism. Previous research has distinguished between two major mechanical effects of ultrasound: cavitation, which refers to the formation and collapse of bubbles, and radiation force, which refers to the transfer of momentum from the ultrasound wave to the tissue that can result in mechanical strain 2 . However, it is still unknown which of these effects dominates the response of the membrane to ultrasound and how that response depends on ultrasound parameters such as frequency and power. Moreover, both of these effects occur as a function of the amplitude of the ultrasound pressure integrated over time, and little is known about effects at high frequencies in the MHz range of oscillating acoustic pressure. We have investigated the direct effect of oscillating pressure on membrane strain with atomistic molecular dynamics simulations. We constructed a lipid bilayer patch of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) lipids solvated in water. After equilibrating the system at physiological conditions, we applied sinusoidal pressure over a range of frequencies from 1 to 43 MHz. Because we are interested in atomic and molecular effects, we computed strain tensors for individual lipid molecules from the coordinate trajectories of every atom with a kinematical algorithm 3 . Our simulation results indicate that (1) strain changes in the membrane were time-locked with the frequency of the pressure wave and (2) increasing the peak pressure increased its effect on strain. These strain effects on the membrane are independent of the effects of cavitation and radiation force and must be included in molecular scale mechanistic explanations of ultrasonic neuromodulation. 1 Blackmore, J., Shrivastava, S., Sallet, J., Butler, C.R., & Cleveland, R.O. Ultrasound Neuromodulation: A Review of Results, Mechanisms, and Safety. Ultrasound Med. Biol. 45(7), 1509-1536 (2019). 2 Menz, M.D., Oralkan, Ö., Khuri-Yakub, P.T., & Baccus, S.A. Precise Neural Stimulation in the Retina Using Focused Ultrasound. J. Neurosci. 33(10), 4550- 4560 (2013). 3 Gullet, P.M., Horstemeyer, M.F., Baskes, M.I., & Fang, H. A deformation gradient tensor and strain tensors for atomistic simulations. Modelling Simul. Mater. Sci. Eng. 16, (2008).

57