Two-Photon Excitation of Azobenzene Photoswitches for Synthetic Optogenetics

Abstract

Synthetic optogenetics is an emerging optical technique that enables users to photocontrol molecules, proteins, and cells in vitro and in vivo. This is achieved by use of synthetic chromophores—denoted photoswitches—that undergo light-dependent changes (e.g., isomerization), which are meticulously designed to interact with unique cellular targets, notably proteins. Following light illumination, the changes adopted by photoswitches are harnessed to affect the function of nearby proteins. In most instances, photoswitches absorb visible light, wavelengths of poor tissue penetration, and excessive scatter. These shortcomings impede their use in vivo. To overcome these challenges, photoswitches of red-shifted absorbance have been developed. Notably, this shift in absorbance also increases their compatibility with two-photon excitation (2PE) methods. Here, we provide an overview of recent efforts devoted towards optimizing azobenzene-based photoswitches for 2PE and their current applications.

Does the chemistry of fungal pigments demand the existence of photoactivated defense strategies in basidiomycetes?

“…While the mushroom is normally white, its flesh rapidly takes on a yellow stain after being damaged [85]. Small molecules containing an azobenzene function are used in optogenetics and as photoswitches of membrane proteins [86,87].…”

Conformable on-skin devices for thermo-electro-tactile stimulation: materials, design, and fabrication

“…[261][262][263] New therapeutic strategies exploit these phenomena, leading to an increasing interest in light-based therapies, such as (i) photodynamic therapy, in which a light source with a specific wavelength activates a photosensitizing agent located in a tumor which causes irreversible photodamage to its tissues; 261 (ii) photo-thermal therapy, that is a minimally-invasive therapy in which photon energy produces heat (also used in cancer treatment); 262 (iii) optogenetics therapies which provide initial genetic modifications of cells in order to express photosensitive traits, subsequently utilized by directly irradiating cells with visible light enabling users to photocontrol molecules, proteins, and cells in vitro and in vivo. 264,265 Most All these therapies can benefit from the use of dermal and transdermal opto-devices as the skin can let trough several wavelengths. For example, a light with a wavelength of 400-500 nm will stop at the epidermal layer, while light with a wavelength longer than 700 nm can reach deeper tissues beyond the dermis.…”

Two-photon absorption and two-photon-induced isomerization of azobenzene compounds

“…The most intense studies concerning two-photon induced isomerization of azobenzenes are related to the elds of photopharmacology and synthetic optogenetics. 21,124 Optogenetics is a novel approach developed for the remote studies of neurons that relies on the use of synthetic light-responsive chromophores to employ photon absorption to modulate structure and function of the target molecule. 124,125 The rst demonstration of the use of AB derivatives toward photo-manipulation was conducted on the nicotinic cholinergic receptor (nACh) in the late 1960s.…”

“…21,124 Optogenetics is a novel approach developed for the remote studies of neurons that relies on the use of synthetic light-responsive chromophores to employ photon absorption to modulate structure and function of the target molecule. 124,125 The rst demonstration of the use of AB derivatives toward photo-manipulation was conducted on the nicotinic cholinergic receptor (nACh) in the late 1960s. 126 To date, signicant modications of AB derivatives have been employed to improve their properties as well as to develop new strategies for AB-mediated photo-control of the receptor and channel function.…”

“…13). 124 Previous works showed that an ionotropic glutamate receptor can be controlled by switching MAG (12) derivatives between two states with violet and green light. 128 The real challenge here was to improve the two-photon absorption cross-section of MAG and for that reason MAG 2P (13) and MAGA 2P (14) were designed and synthesized.…”