Optogenetics combines light and genetics to enable precise control of living cells, tissues, and organisms with tailored functions. Optogenetics has the advantages of noninvasiveness, rapid responsiveness, tunable reversibility, and superior spatiotemporal resolution. Following the initial discovery of microbial opsins as light-actuated ion channels, a plethora of naturally occurring or engineered photoreceptors or photosensitive domains that respond to light at varying wavelengths has ushered in the next chapter of optogenetics. Through protein engineering and synthetic biology approaches, genetically-encoded photoswitches can be modularly engineered into protein scaffolds or host cells to control a myriad of biological processes, as well as to enable behavioral control and disease intervention in vivo. Here, we summarize these optogenetic tools on the basis of their fundamental photochemical properties to better inform the chemical basis and design principles. We also highlight exemplary applications of opsin-free optogenetics in dissecting cellular physiology (designated "optophysiology"), and describe the current progress, as well as future trends, in wireless optogenetics, which enables remote interrogation of physiological processes with minimal invasiveness. This review is anticipated to spark novel thoughts on engineering next-generation optogenetic tools and devices that promise to accelerate both basic and translational studies.

中文翻译：

---

光生理学：用光遗传学照亮细胞生理学

光遗传学结合了光和遗传学，可以精确控制具有定制功能的活细胞、组织和生物体。光遗传学具有无创性、快速响应性、可调可逆性和优越的时空分辨率等优点。随着微生物视蛋白作为光驱动离子通道的初步发现，大量天然存在或工程化的光感受器或对不同波长的光作出反应的光敏结构域迎来了光遗传学的下一章。通过蛋白质工程和合成生物学方法，基因编码的光开关可以被模块化设计到蛋白质支架或宿主细胞中，以控制无数的生物过程，以及实现体内行为控制和疾病干预。这里，我们根据它们的基本光化学特性总结了这些光遗传学工具，以更好地了解化学基础和设计原则。我们还强调了无视蛋白光遗传学在解剖细胞生理学（称为“光生理学”）中的典型应用，并描述了无线光遗传学的当前进展以及未来趋势，无线光遗传学能够以最小的侵入性远程询问生理过程。预计这篇综述将引发关于工程下一代光遗传学工具和设备的新想法，这些工具和设备有望加速基础研究和转化研究。我们还强调了无视蛋白光遗传学在解剖细胞生理学（称为“光生理学”）中的典型应用，并描述了无线光遗传学的当前进展以及未来趋势，无线光遗传学能够以最小的侵入性远程询问生理过程。预计这篇综述将引发关于工程下一代光遗传学工具和设备的新想法，这些工具和设备有望加速基础研究和转化研究。我们还强调了无视蛋白光遗传学在解剖细胞生理学（称为“光生理学”）中的典型应用，并描述了无线光遗传学的当前进展以及未来趋势，无线光遗传学能够以最小的侵入性远程询问生理过程。预计这篇综述将引发关于工程下一代光遗传学工具和设备的新想法，这些工具和设备有望加速基础研究和转化研究。