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.
Highlights
Photoreceptors are protein light-detectors that allow the cell/organism to respond to its environment [1]
The functional outcome of blocking this potassium channel is robust neuronal excitability and action potential firing. This effect was completely reversed by near-UV illumination (~400 nm), pushing the photoswitch back to -cis, a much shorter form, thereby physically removing the blocker away from the pore leading to immediate silencing of the neuron [30]
Two trans-active diffusible photoswitches were designed based on a C2-bridged azobenzene, denoted locked-azobenzene (LAB) [82] or Glu_brAzo [72]. Both photoswitches bear a glutamate moiety as ligand, intended for activation of glutamate receptors, and exhibit highly similar structural and spectral properties (Figure 3)
Summary
Photoreceptors are protein light-detectors that allow the cell/organism to respond to its environment [1]. Some have been fashioned to mechanically restructure membrane lipids or DNA molecules [13,14,15], to act as light-activated forceps [16] or to include pharmacological agents (e.g., pore-blockers) to block, agonize, or antagonize receptors, ion channels, or enzymes (Figure 1b) ( see reviews [9,17,18]). It is noteworthy to mention that this method dates back to the late 1960s (Figure 2) [19], it has gained momentum in early 2000 owing to critical advances in chemistry, biology, and imaging methods.
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