Dynamic Response of Model Lipid Membranes to Ultrasonic Radiation Force

Abstract

Low-intensity ultrasound can modulate action potential firing in neurons in vitro and in vivo. It has been suggested that this effect is mediated by mechanical interactions of ultrasound with neural cell membranes. We investigated whether these proposed interactions could be reproduced for further study in a synthetic lipid bilayer system. We measured the response of protein-free model membranes to low-intensity ultrasound using electrophysiology and laser Doppler vibrometry. We find that ultrasonic radiation force causes oscillation and displacement of lipid membranes, resulting in small (<1%) changes in membrane area and capacitance. Under voltage-clamp, the changes in capacitance manifest as capacitive currents with an exponentially decaying sinusoidal time course. The membrane oscillation can be modeled as a fluid dynamic response to a step change in pressure caused by ultrasonic radiation force, which disrupts the balance of forces between bilayer tension and hydrostatic pressure. We also investigated the origin of the radiation force acting on the bilayer. Part of the radiation force results from the reflection of the ultrasound from the solution/air interface above the bilayer (an effect that is specific to our experimental configuration) but part appears to reflect a direct interaction of ultrasound with the bilayer, related to either acoustic streaming or scattering of sound by the bilayer. Based on these results, we conclude that synthetic lipid bilayers can be used to study the effects of ultrasound on cell membranes and membrane proteins.

Frequency Dependence of Ultrasound Neurostimulation in the Mouse Brain

“…While the amplitude of particle displacement will be relatively small compared to the wavelength of the ultrasound, the displacements could still be sufficient to perturb subcellular neural structures (Jolesz and Hynynen 2008). Specifically, these mechanisms could involve deforming the lipid bilayer (Prieto et al 2013), acting on the mechanisms for synaptic vesicle release (Tyler 2011), and/or activating stretch-sensitive ion channels (Bystritsky et al 2011; Heureaux et al 2014; Tyler 2011). In fact, several mechanosensitive ion channels have been found in the transcriptome of mouse cortical neurons, including TREK-1, TREK-2, TRAAK, and members of the TRP channel family (Zhang et al 2014).…”

Neuromodulation with transcranial focused ultrasound

“…This hypothesis has not, thus far, found robust experimental support. 50,51 A relatively recent model based on this idea, “intramembrane cavitation,” 29,47,48 predicts a profound drop of the membrane potential in response to FUS onset. The proposed drop measures ≥ 100 mV in the hyperpolarizing direction and can be observed for a period of several milliseconds.…”

“…Thus far, such a marked drop in membrane voltage in response to FUS has not been confirmed in direct cellular recordings. 30,50,58 …”

Offline impact of transcranial focused ultrasound on cortical activation in primates

“…In vitro recordings have identified several mechanisms by which ultrasound stimulation could affect neurons. It has been proposed that the sound pressure wave exerts a mechanical effect on neuronal activity through ion channel gating [13][14][15] . In the macaque, its application over the frontal eye field (FEF) affects the same aspects of oculomotor behavior that are compromised by FEF lesion, whilst leaving intact those aspects of oculomotor behavior that are unaffected by FEF lesion 16 .…”