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.

Highlights

  • Ultrasound has a wide range of effects on biological tissue, many of which are not fully understood

  • Transducer arrays that transmit ultrasound through the human skull have been implemented in high-intensity focused ultrasound surgery [12,13,14,15], and it has been proposed that this technology could be adapted to deliver low-intensity ultrasound for the treatment of neurological disorders [5,10]

  • We investigated the mechanical effects of low-intensity ultrasound on lipid bilayers using electrophysiology and optical vibrometry

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Summary

Introduction

Ultrasound has a wide range of effects on biological tissue, many of which are not fully understood. The motivation for the present work, is the modulation of neural activity with low-intensity ultrasound [1,2,3]. Research on the effects of ultrasound on excitable tissue dates back to the 1920s [4], several recent results have revived interest in this phenomenon. Reversible changes in action potential frequency in response to low-intensity ultrasound (on the order of 0.1–10 W/cm2) have been observed in vitro [5,6] and in vivo [7,8,9,10,11]. Transducer arrays that transmit ultrasound through the human skull have been implemented in high-intensity focused ultrasound surgery [12,13,14,15], and it has been proposed that this technology could be adapted to deliver low-intensity ultrasound for the treatment of neurological disorders [5,10]

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