Sensing Senses: Optical Biosensors to Study Gustation

Abstract

The five basic taste modalities, sweet, bitter, umami, salty and sour induce changes of Ca2+ levels, pH and/or membrane potential in taste cells of the tongue and/or in neurons that convey and decode gustatory signals to the brain. Optical biosensors, which can be either synthetic dyes or genetically encoded proteins whose fluorescence spectra depend on levels of Ca2+, pH or membrane potential, have been used in primary cells/tissues or in recombinant systems to study taste-related intra- and intercellular signaling mechanisms or to discover new ligands. Taste-evoked responses were measured by microscopy achieving high spatial and temporal resolution, while plate readers were employed for higher throughput screening. Here, these approaches making use of fluorescent optical biosensors to investigate specific taste-related questions or to screen new agonists/antagonists for the different taste modalities were reviewed systematically. Furthermore, in the context of recent developments in genetically encoded sensors, 3D cultures and imaging technologies, we propose new feasible approaches for studying taste physiology and for compound screening.

An alternative pathway for sweet sensation: possible mechanisms and physiological relevance

“…Due to the ubiquitous expression of the sweet-taste receptor ("Sweet-taste transduction in extraoral tissues"), tissuespecific knockout models are necessary to better understand the mechanism and role of the alternative sweet pathway. Specific behavioral tests, ex vivo and in vivo live cell imaging experiments [202] performed in such transgenic animals may largely contribute to the dissection of the alternative sweettransduction pathway.…”

“…In such human-derived taste cells, the different genes involved in the sweet-signaling pathways could be silenced via RNA-interference. Furthermore, these cells can be engineered to express genetically encoded fluorescent sensors to measure Ca 2+ signaling, glucose transport, and its metabolism via live-cell imaging [27,68,86,201,202]. Thus, the employment of human-derived taste cells and 3D cultures may provide a more physiological context to study human gustation [201,202].…”

“…Accordingly, the cases of type 2 diabetes, obesity, and cardiovascular diseases are steadily increasing [29,32] rendering the understanding of sweet-taste transduction critical for their prevention and treatment. Although the primary "sweet-taste receptor" was already identified in 2001 [14,124,142,163,185,203,211,252], human sweet-taste transduction is still not fully understood, as taste physiology has been mainly studied in rodents and heterologous systems (for review, [202]). Furthermore, human sweettaste sensation and preference vary with age [212], genetics [85,231], sex [329], diseases [212,223,269,293], and temperature [161,306].…”

Sweet Taste Is Complex: Signaling Cascades and Circuits Involved in Sweet Sensation

“…An alternative experimental system consists in mammalian cell lines heterologously expressing the human sweet taste receptor and its downstream signaling molecules. In this case however, the native cellular background and the niche are missing (von Molitor et al, 2020b). Thus, a new approach, based on organoids derived from mouse taste progenitor cells, may resemble more closely the native environment (Ren et al, 2009(Ren et al, , 2010(Ren et al, , 2014(Ren et al, , 2017 and organoids could be theoretically also generated from human papillae.…”

Detection of Bitter Taste Molecules Based on Odorant-Binding Protein-Modified Screen-Printed Electrodes

“…Recently, biosensors for the detection of bitter molecules are usually constructed based on gustatory tissue cells and bitter receptors. 5 − 7 However, the sensitive tissue cells that are extracted and cultivated with a complex process are highly dependent on the culture environments such as temperature and nutrition, making them impractical for applications in the biosensors. Due to high specificity, the bitter taste receptors such as T2R1 and T2R4 are the most desirable bitter-sensitive materials, which are usually produced from taste tissue cells and accessible for quantitative immobilization on electrodes to improve the repeatability.…”