Cholesterol Functionalization of Gold Nanoparticles Enhances Photoactivation of Neural Activity

Gold nanoparticles (AuNPs) attached to the extracellular leaflet of the plasma membrane of neurons can enable the generation of action potentials (APs) in response to brief pulses of light. Recently described techniques to stably bind AuNP bioconjugates directly to membrane proteins (ion channels) i...

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Published in:ACS chemical neuroscience 2019-03, Vol.10 (3), p.1478-1487
Main Authors: Carvalho-de-Souza, Joao L, Nag, Okhil K, Oh, Eunkeu, Huston, Alan L, Vurgaftman, Igor, Pepperberg, David R, Bezanilla, Francisco, Delehanty, James B
Format: Article
Language:English
Subjects:
Animals
Cell Membrane - drug effects
Cell Membrane - metabolism
Cholesterol - administration & dosage
Ganglia, Spinal - drug effects
Ganglia, Spinal - metabolism
Gold - administration & dosage
HEK293 Cells
Humans
Metal Nanoparticles - administration & dosage
Neurons - drug effects
Neurons - metabolism
Photic Stimulation - methods
Rats
Rats, Sprague-Dawley
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Summary:Gold nanoparticles (AuNPs) attached to the extracellular leaflet of the plasma membrane of neurons can enable the generation of action potentials (APs) in response to brief pulses of light. Recently described techniques to stably bind AuNP bioconjugates directly to membrane proteins (ion channels) in neurons enable robust AP generation mediated by the photoexcited conjugate. However, a strategy that binds the AuNP to the plasma membrane in a non protein-specific manner could represent a simple, single-step means of establishing light-responsiveness in multiple types of excitable neurons contained in the same tissue. On the basis of the ability of cholesterol to insert into the plasma membrane, here we test whether AuNP functionalization with linear dihydrolipoic acid-poly­(ethylene) glycol (DHLA-PEG) chains that are distally terminated with cholesterol (AuNP–PEG–Chol) can enable light-induced AP generation in neurons. Dorsal root ganglion (DRG) neurons of rat were labeled with 20 nm diameter spherical AuNP–PEG–Chol conjugates wherein ∼30% of the surface ligands (DHLA-PEG-COOH) were conjugated to PEG–Chol. Voltage recordings under current-clamp conditions showed that DRG neurons labeled in this manner exhibited a capacity for AP generation in response to microsecond and millisecond pulses of 532 nm light, a property attributable to the close tethering of AuNP–PEG–Chol conjugates to the plasma membrane facilitated by the cholesterol moiety. Light-induced AP and subthreshold depolarizing responses of the DRG neurons were similar to those previously described for AuNP conjugates targeted to channel proteins using large, multicomponent immunoconjugates. This likely reflected the AuNP–PEG–Chol’s ability, upon plasmonic light absorption and resultant slight and rapid heating of the plasma membrane, to induce a concomitant transmembrane depolarizing capacitive current. Notably, AuNP–PEG–Chol delivered to DRG neurons by inclusion in the buffer contained in the recording pipet/electrode enabled similar light-responsiveness, consistent with the activity of AuNP–PEG–Chol bound to the inner (cytofacial) leaflet of the plasma membrane. Our results demonstrate the ability of AuNP–PEG–Chol conjugates to confer timely stable and direct responsiveness to light in neurons. Further, this strategy represents a general approach for establishing excitable cell photosensitivity that could be of substantial advantage for exploring a given tissue’s suitability for AuNP-mediated pho
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.8b00486