Bioluminescence: a versatile technique for imaging cellular and molecular features

Abstract

Bioluminescence is a ubiquitous imaging modality for visualizing biological processes in vivo. This technique employs visible light and interfaces readily with most cell and tissue types, making it a versatile technology for preclinical studies. Here we review basic bioluminescence imaging principles, along with applications of the technology that are relevant to the medicinal chemistry community. These include noninvasive cell tracking experiments, analyses of protein function, and methods to visualize small molecule metabolites. In each section, we also discuss how bioluminescent tools have revealed insights into experimental therapies and aided drug discovery. Last, we highlight the development of new bioluminescent tools that will enable more sensitive and multi-component imaging experiments and, thus, expand our broader understanding of living systems.

In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease

“…S4A). Similar flash-type light emission kinetics are observed with D-luciferin, where the decay results from enzyme inhibition by luciferin/luciferase reaction byproducts (41,42,44). The similarity in light emission kinetics in the presence and absence of copper treatment suggests that bioluminescence results from luciferase reaction with the same substrate, namely D-luciferin.…”

“…Luciferin-based bioluminescence imaging is an attractive modality for in vivo use owing to its low background signal, efficient photon production, and good tissue penetration of its red-shifted emission (40)(41)(42). Moreover, impressive advances in luciferase engineering and ease of targeting by genetic encoding permit the broad use of such reporters for in vivo imaging with cell and tissue specificity (41,43,44).…”

“…Luciferin-based bioluminescence imaging is an attractive modality for in vivo use owing to its low background signal, efficient photon production, and good tissue penetration of its red-shifted emission (40)(41)(42). Moreover, impressive advances in luciferase engineering and ease of targeting by genetic encoding permit the broad use of such reporters for in vivo imaging with cell and tissue specificity (41,43,44). We and others have developed caged luciferins, which are enzymeinert luciferin derivatives that are chemically unmasked to the luciferin substrate in the presence of an analyte or biochemical event of interest for subsequent enzymatic generation of light (45)(46)(47)(48)(49)(50); in particular, our laboratory has used this approach to develop bioluminescent H 2 O 2 reporters (45,47).…”

High-throughput Live Cell Imaging and Analysis for Temporal Reaction of G Protein-coupled Receptor Based on Split Luciferase Fragment Complementation

“…In addition, luciferase types using substrate D-luciferin show stable luminescence photon counts in sustained measurement. 13 Therefore, ELuc, which is an extremely bright luciferase using D-luciferin, was chosen for the imaging assay. 14 In an earlier study using ELuc, we demonstrated the potential of a split luciferase fragment complementation assay with GPCR protein, β2-adrenergic receptor (ADRB2), and β-arrestin2.…”

Sensors at the micro-scale

“…used as "microbial biosensors" [8], for example, for detection of toxic materials. Also, the ability to track the light-emitting cells within an organism provides powerful in vivo imaging technology [9]. Bioluminescence technologies have been applied in research on drugs, cancer, bacterial infectious diseases, etc.…”