title: Photosensitivity of neurons enabled by cell-targeted gold nanoparticles.
abstract: Unmodified neurons can be directly stimulated with light to produce action potentials, but such techniques have lacked localization of the delivered light energy. Here we show that gold nanoparticles can be conjugated to high-avidity ligands for a variety of cellular targets. Once bound to a neuron, these particles transduce millisecond pulses of light into heat, which changes membrane capacitance, depolarizing the cell and eliciting action potentials. Compared to non-functionalized nanoparticles, ligand-conjugated nanoparticles highly resist convective washout and enable photothermal stimulation with lower delivered energy and resulting temperature increase. Ligands targeting three different membrane proteins were tested; all showed similar activity and washout resistance. This suggests that many types of ligands can be bound to nanoparticles, preserving ligand and nanoparticle function, and that many different cell phenotypes can be targeted by appropriate choice of ligand. The findings have applications as an alternative to optogenetics and potentially for therapies involving neuronal photostimulation.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: João L
authors.initials: JL
authors.lastname: Carvalho-de-Souza
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Treger
authors.affiliation: Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Bobo
authors.initials: B
authors.lastname: Dang
authors.affiliation: Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Stephen B H
authors.initials: SB
authors.lastname: Kent
authors.affiliation: Lions of Illinois Eye Research Institute, Illinois Eye and Ear Infirmary, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA. Electronic address: davipepp@uic.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Pepperberg
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: fbezanilla@uchicago.edu.
authors.forename: Francisco
authors.initials: F
authors.lastname: Bezanilla
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004307:Dose-Response Relationship, Radiation; D005727:Ganglia, Spinal / Q000166:cytology; D006046:Gold; D008024:Ligands; D008564:Membrane Potentials / Q000528:radiation effects*; D053758:Nanoparticles / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D055095:Optics and Photonics; D051381:Rats; D013997:Time Factors
chemical_list: D008024:Ligands; D006046:Gold