Effects of Low Intensity Focused Ultrasound on Liposomes Containing Channel proteins

Meghedi Babakhanian, Limin Yang, Bryan Nowroozi, George Saddik, Lilian Boodaghians, Paul Blount, Warren Grundfest

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

The ability to reversibly and non-invasively modulate region-specific brain activity in vivo suggests Low Intensity Focused Ultrasound (LIFU) as potential therapeutics for neurological dysfunctions such as epilepsy and Parkinson’s disease. While in vivo studies provide evidence of the bioeffects of LIFU on neuronal activity, they merely hint at potential mechanisms but do not fully explain how this technology achieves these effects. One potential hypothesis is that LIFU produces local membrane depolarization by mechanically perturbing the neuronal cell membrane, or activating channels or other proteins embedded in the membrane. Proteins that sense mechanical perturbations of the membrane, such as those gated by membrane tension, are prime candidates for activating in response to LIFU and thus leading to the neurological responses that have been measured. Here we use the bacterial mechanosensitive channel MscL, which has been purified and reconstituted in liposomes, to determine how LIFU may affect the activation of this membrane-tension gated channel. Two bacterial voltage-gated channels, KvAP and NaK2K F92A channels were also studied. Surprisingly, the results suggest that ultrasound modulation and membrane perturbation does not induce channel gating, but rather induces pore formation at the membrane protein-lipid interface. However, in vesicles with high MscL mechanosensitive channel concentrations, apparent decreases in pore formation are observed, suggesting that this membrane-tension-sensitive protein may serve to increase the elasticity of the membrane, presumably because of expansion of the channel in the plane of the membrane independent of channel gating.

Original languageEnglish (US)
Article number17250
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

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