Photosensitivity of Neurons Enabled by Cell-Targeted Gold Nanoparticles

Abstract

Summary 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.

Thermal Transients Excite Neurons through Universal Intramembrane Mechanoelectrical Effects

“…This study explored the effects of temperature changes on membrane capacitance and its associated currents in a joint attempt to clarify the experimental results of a key recent study [16] and to pave the way towards predictive modeling of INS [2][3][4][5][6][7][8][9][10][11][12][13][14][15] and other thermal neurostimulation techniques [18][19][20], which could potentially facilitate the development of more advanced and multimodal methods for neural circuit control. Another key motivation to pursue this problem came from our noting the very similar temperature-related capacitance rates of change observed in very different model systems [ Fig.…”

“…The new mechanoelectrical thermal activation (META) models calculate the effect of temperature change on the membrane electrical parameters directly and explicitly (rather than implicitly), and are found to both qualitatively and quantitatively predict empirical findings on thermal membrane capacitance increases [16,19,20,24], unraveling the two underlying sources for thermal membrane currents, and making it possible to indirectly estimate from neural stimulation results a significant new quantity, the membrane surface charge difference.…”

“…A multitude of INS-related studies explored the ability of short-wave infrared (IR) pulses to stimulate neural structures including peripheral [3,4] and cranial nerves [5][6][7][8][9][10], retinal and cortical neurons [10][11][12], as well as cardiomyocytes [13,14]. It is stipulated that the INS phenomenon is mediated by temperature transients induced by IR absorption [15][16][17]; such transients can alternatively be induced using other forms of photoabsorption [18][19][20], or potentially by any other physical form of thermal neurostimulation that can be driven rapidly enough [21,22]. Shapiro et al [16] showed that these rapid temperature variations are directly accompanied by changes in the cell membrane's capacitance and resulting displacement currents which are unrelated to specific ionic channels; their findings on the thermal capacitance increase have been supported by experiments from several additional groups [19,20,[23][24][25].…”

“…It is stipulated that the INS phenomenon is mediated by temperature transients induced by IR absorption [15][16][17]; such transients can alternatively be induced using other forms of photoabsorption [18][19][20], or potentially by any other physical form of thermal neurostimulation that can be driven rapidly enough [21,22]. Shapiro et al [16] showed that these rapid temperature variations are directly accompanied by changes in the cell membrane's capacitance and resulting displacement currents which are unrelated to specific ionic channels; their findings on the thermal capacitance increase have been supported by experiments from several additional groups [19,20,[23][24][25]. Shapiro et al [16] also developed a theoretical model where the temperature elevation was seen to give rise to membrane capacitance increase at the membrane's boundary regions (see also Liu et al [26] and Rabbit et al [27]).…”

Light‐Patterned RNA Interference of 3D‐Cultured Human Embryonic Stem Cells

“…NIR laser irradiation was performed through z-stacks of the cell mass with 1.4 µm intervals, and each z-stack (512 × 512 pixels) was scanned line-by-line Biological processes are stimulated by various molecular and physical signals orchestrated in space and time. [1][2][3][4] Tissue and organ generation in vitro for transplant therapy and disease modeling for drug screening [5] are especially demanding for precise control over 3D patterning of different cell types. [2,4,6,7] Advances in this area include the controlled differentiation of pluripotent or multipotent stem cells cultured in 3D matrices followed by self-organization into tissues in vitro.…”