Odorant Transport Research Articles

Odorant Binding Proteins Facilitate the Gas-Phase Uptake of Odorants Through the Nasal Mucus.

Mammalian odorant binding proteins (OBPs) have long been suggested to transport hydrophobic odorant molecules through the aqueous environment of the nasal mucus. While the function of OBPs as odorant transporters is supported by their hydrophobic beta-barrel structure, no rationale has been provided on why and how these proteins facilitate the uptake of odorants from the gas phase. Here, a multi-scale computational approach validated through available high-resolution spectroscopy experiments reveals that the conformational space explored by carvone inside the binding cavity of porcine OBP (pOBP) is much closer to the gas than the aqueous phase, and that pOBP effectively manages to transport odorants by lowering the free energy barrier of odorant uptake. Understanding such perireceptor events is crucial to fully unravel the molecular processes underlying the olfactory senseand move towards the development of protein-based biomimetic sensor units that can serve as artificial noses.

How does vortex dynamics help undulating bodies spread odor?

In this paper, we examine the coupling between odor dynamics and vortex dynamics around undulating bodies, with a focus on bio-inspired propulsion mechanisms. Utilizing computational fluid dynamics simulations with an in-house immersed boundary method solver, we investigate how different waveform patterns, specifically carangiform and anguilliform, influence the dispersion of chemical cues in both water and air environments. Our findings reveal that vortex dynamics significantly impact the overall trajectory of odor spots, although the alignment between odor spots and coherent flow structures is not always precise. We also evaluate the relative contributions of diffusion and convection in odor transport, showing that convection dominates in water, driven by higher Schmidt numbers, while diffusion plays a more prominent role alongside convection in air. Additionally, the anguilliform waveform generally produces stronger and farther-reaching chemical cues compared to carangiform swimmers. The critical roles of Strouhal number and Reynolds number in determining the efficiency of odor dispersion are also explained, offering insights that could enhance the design of more efficient, adaptive, and intelligent autonomous underwater vehicles by integrating sensory and hydrodynamic principles inspired by fish locomotion.

Olfactory navigation in fluctuating environments

We humans move around in the world, guided largely by light and sound. Many cohabitants of our planet, however, predominantly use their chemical senses to navigate a rich landscape. Light and sound propagate with predictable geometric precision, and animals in particular have evolved ways to exploit these physical principles. Odors, on the other hand, are at the mercy of the carrier medium, air or water, for long distance transport, which can quickly become turbulent and unpredictable. Nevertheless, animals have found ways to navigate these fickle features to chase mates, find food or return home. Understanding the physics of odor transport can help rationalize the strategies animals use for navigation and guide studies of how the corresponding algorithms are implemented by their brains and bodies.

Odorant transport in a hagfish

Odorant transport is of fundamental and applied importance. Using computational simulations, we studied odorant transport in an anatomically accurate model of the nasal passage of a hagfish (probably Eptatretus stoutii). We found that ambient water is sampled widely, with a significant ventral element. Additionally, there is a bilateral element to olfactory flow, which enters the single nostril in two narrow, laminar streams that are then split prior to the nasal chamber by the anterior edge of the central olfactory lamella. An appendage on this lamella directs a small portion (10–14%) of the overall nasal flow to the olfactory sensory channels. Much of the remaining flow is diverted away from the sensory channels by two peripheral channels. The anterior edge of the central olfactory lamella, together with a jet-impingement mechanism, disperses flow over the olfactory surfaces. Diffusion of odorant from bulk water to the olfactory surfaces is facilitated by the large surface area:volume ratio of the sensory channels, and by a resistance-based hydrodynamic mechanism that leads to long residence times (up to 4.5 s) in the sensory channels. With increasing volumetric flow rate, the rate of odorant transfer to the olfactory surfaces increases, but the efficiency of odorant uptake decreases, falling in the range 2–6%. Odorant flux decreases caudally across the olfactory surfaces, suggesting in vivo a preponderance of olfactory sensory neurons on the anterior part of each olfactory surface. We conclude that the hagfish has a subtle anatomy for locating and capturing odorant molecules.

A new surgical technique to increase airflow in the olfactory cleft: superior turbinate lateralization procedure.

The olfactory cleft (OC) is the most important anatomical site for the maintenance of olfactory function. Obstruction of airflow in the OC by various conditions, such as inflammation, leads to poor olfactory function. Therefore, it is important to increase OC airflow while performing endoscopic sinus surgery (ESS). However, no technique to increase airflow has yet been established. We designed a superior turbinate lateralization (STL) procedure that displaces the entire ST bone laterally by eliminating the connection between the posterior ST and the anterior wall of the sphenoid sinus. The effect of the STL procedure was investigated in terms of anatomy and olfactory function. ESS with the STL procedure was performed on seven patients with chronic rhinosinusitis and nasal polyps. The cross-sectional area of the OC at 3months postoperatively was significantly larger than that before ESS. In addition, the Open Essence test and questionnaires revealed significantly improvements in sense of smell. Airflow in the OC was significantly higher in STL procedure group than in the non-STL procedure group. The STL procedure enlarges the bony framework of the OC, and by increasing OC airflow, facilitates the transport of odorants to the olfactory epithelium, thereby improving olfactory perception.

Is the mouse nose a miniature version of a rat nose? A computational comparative study

Background and objectiveAlthough the mouse is a widely used animal model in biomedical research, there are few published studies on its nasal aerodynamics, potentially due to its small size. It is not appropriate to assume that mice and rats' nasal structure and airflow characteristics are the same because the ratio of nasal surface area to nasal volume and body weight is much higher in a mouse than in a rat. The aim of this work is to use anatomically accurate image-based computational fluid dynamic modeling to quantitatively reveal the characteristics of mouse nasal airflow and mass transport that haven't been detailed before and find key differences to that of rat nose, which will deepen our understanding of the mouse's physiological functions. MethodsWe created an anatomically accurate 3D computational nasal model of a B6 mouse using postmortem high-resolution micro-CT scans and simulated the airflow distribution and odor transport patterns under restful breathing conditions. The deposition pattern of airborne particles was also simulated and validated against experimental data. In addition, we calculated the gas chromatograph efficiency of odor transport in the mouse employing the theoretical plate concept and compared it with previous studies involving cat and rat models. ResultsSimilar to the published rat model, respiratory and olfactory flow regimes are clearly separated in the mouse nasal cavity. A high-speed dorsal medial (DM) stream was observed, which enhances the delivery speed and efficiency of odor to the ethmoid (olfactory) recess (ER). The DM stream split into axial and secondary paths in the ER. However, the secondary flow in the mouse is less extensive than in the rat. The gas chromatograph efficiency calculations suggest that the rat may possess a moderately higher odorant transport efficiency than that of the mouse due to its more complex ethmoid recess structure and extensive secondary flow. However, the mouse's nasal structure seems to adapt better to varying airflow velocity. ConclusionsDue to the inherent structural disparities, the rat and mouse models exhibit moderate differences in airflow and mass transport patterns, potentially impacting their olfaction and other behavioral habits.

Physical properties of odorants affect behavior of trained detection dogs during close-quarters searches

Trained detection dogs have a unique ability to find the sources of target odors in complex fluid environments. How dogs derive information about the source of an odor from an odor plume comprised of odorants with different physical properties, such as diffusivity, is currently unknown. Two volatile chemicals associated with explosive detection, ammonia (NH3, derived from ammonium nitrate-based explosives) and 2-ethyl-1-hexanol (2E1H, associated with composition C4 plastic explosives) were used to ascertain the effects of the physical properties of odorants on the search behavior and motion of trained dogs. NH3 has a diffusivity 3.6 times that of 2E1H. Fourteen civilian detection dogs were recruited to train on each target odorant using controlled odor mimic permeation systems as training aids over 6 weeks and then tested in a controlled-environment search trial where behavior, motion, and search success were analyzed. Our results indicate the target-odorant influences search motion and time spent in the stages of searching, with dogs spending more time in larger areas while localizing NH3. This aligns with the greater diffusivity of NH3 driving diffusion-dominated odor transport when dogs are close to the odor source in contrast to the advection-driven transport of 2E1H at the same distances.

Wings and whiffs: Understanding the role of aerodynamics in odor-guided flapping flight

Odor-guided navigation is an indispensable aspect of flying insects' behavior, facilitating crucial activities such as foraging and mating. The interaction between aerodynamics and olfaction plays a pivotal role in the odor-guided flight behaviors of insects, yet the interplay of these two functions remains incompletely understood. In this study, we developed a fully coupled three-way numerical solver, which solves the three-dimensional Navier–Stokes equations coupled with equations of motion for the passive flapping wings, and the odorant advection–diffusion equation. This numerical solver is applied to investigate the unsteady flow field and the odorant transport phenomena of a fruit fly model in odor-guided upwind surge flight over a broad spectrum of reduced frequencies (0.325–1.3) and Reynolds numbers (90–360). Our results uncover a complex dependency between flight velocity and odor plume perception, modulated by the reduced frequency of flapping flight. At low reduced frequencies, the flapping wings disrupt the odor plume, creating a saddle point of air flow near the insect's thorax. Conversely, at high reduced frequencies, the wing-induced flow generates a stagnation point, in addition to the saddle point, that alters the aerodynamic environment around the insect's antennae, thereby reducing odor sensitivity but increasing the sampling range. Moreover, an increase in Reynolds number was found to significantly enhance odor sensitivity due to the synergistic effects of greater odor diffusivity and stronger wing-induced flow. These insights hold considerable implications for the design of bio-inspired, odor-guided micro air vehicles in applications like surveillance and detection.

A pilot numerical study of odorant transport to the olfactory region during sensory evaluations following ISO 16000-28

We numerically analyzed odorant transportation from a sniffing device (funnel) to the olfactory region of the nasal cavity during breathing. We followed the procedure for the perceived air quality evaluations described in the ISO 16000-28 standard, and used acetone defined as the standard test substance for pi-scale evaluations in this standard; we also used ammonia and acetic acid, as acetone also emitted by humans. We modelled two breathing conditions: normal breathing (through nose) and sniffing. We evaluated olfactory receptor access under these breathing conditions. The acetone absorption flux to the olfactory epithelial tissues was analyzed using a computer-simulated person with a numerical respiratory tract model and a physiologically based pharmacokinetic model that was used to validate the prediction accuracy. The absorption flux and sensible/latent heat flux to the olfactory epithelial tissue were analyzed quantitatively. We also analyzed the impact of flow through the ortho- and retro-nasal pathways on the absorption flux to the olfactory region. The transient inhalation/exhalation airflow profile, breathing, and sniffing conditions had a significant impact on the absorption flux to the olfactory region of the nasal cavity. We observed two peaks of odorant absorption flux in one breath one during inhalation and one during exhalation. For example, 0.5μg/(m2s) of peak acetone absorption flux in the olfactory region during inhalation and 0.1μg/(m2s) during exhalation was observed.

Expression and functional analysis of an odorant binding protein PopeOBP16 from Phthorimaea operculella (Zeller)

Odorant binding proteins (OBPs) are essential proteins in the peripheral olfactory system, responsible for odorant recognition and transport to olfactory receptors. Phthorimaea operculella (potato tuber moth) is an important oligophagous pest on Solanaceae crops in many countries and regions. PopeOBP16 is one of the OBPs in potato tuber moth. This study examined the expression profiles of PopeOBP16. The results of qPCR indicated that PopeOBP16 was highly expressed in the antennae of adults, especially in males, suggesting that it may be involved in odor recognition in adults. The electroantennogram (EAG) was used to screen candidate compounds with the antennae of P. operculella. The relative affinities of PopeOBP16 to 27 host volatiles and two sex pheromone components with the highest relative EAG responses were examined with competitive fluorescence-based binding assays. PopeOBP16 had the strongest binding affinity with the plant volatiles: nerol, 2-phenylethanol, linalool, 1,8-cineole, benzaldehyde, β-pinene, d-limonene, terpinolene, α-terpinene, and the sex pheromone component trans-4, cis-7, cis-10-tridecatrien-1-ol acetate. The results provide a foundation for further research into the functioning of the olfactory system and the potential development of green chemistry for control of the potato tuber moth.

Ligand Binding Properties of Odorant-Binding Protein OBP5 from Mus musculus.

Odorant-binding proteins (OBPs) are abundant soluble proteins secreted in the nasal mucus of a variety of species that are believed to be involved in the transport of odorants toward olfactory receptors. In this study, we report the functional characterization of mouse OBP5 (mOBP5). mOBP5 was recombinantly expressed as a hexahistidine-tagged protein in bacteria and purified using metal affinity chromatography. The oligomeric state and secondary structure composition of mOBP5 were investigated using gel filtration and circular dichroism spectroscopy. Fluorescent experiments revealed that mOBP5 interacts with the fluorescent probe N-phenyl naphthylamine (NPN) with micromolar affinity. Competitive binding experiments with 40 odorants indicated that mOBP5 binds a restricted number of odorants with good affinity. Isothermal titration calorimetry (ITC) confirmed that mOBP5 binds these compounds with association constants in the low micromolar range. Finally, protein homology modeling and molecular docking analysis indicated the amino acid residues of mOBP5 that determine its binding properties.

A Nasal Aerodynamics Perspective of Retronasal Olfaction: Rodents vs. Humans.

Odor perception can be achieved through ortho or retronasal routes, with the latter being an important component of flavor perception. There are significant olfactory differences that exist between rats and humans and by understanding the role of structural differences, further insight can be gained into the mechanism of odorant perception via ortho or retronasal routes. 3D human and rat (Sprague Dawley) computational models were used to investigate nasal anatomy impact on ortho vs. retronasal odorant transport to the olfactory epithelium. The nasal pharynx region was modified for human and rat models to probe nasal structure impact on ortho vs retro olfaction. 65 odorant absorption rates to the olfactory epithelium were extracted from each model. For human, the retronasal route provided higher peak odorant absorption compared to orthonasal route (left: 90% higher, right: 45% higher), but substantially lowered peak absorption for rat (medial: 97% lower, lateral: 75% lower). For both models, anatomical modification had minimal impact to orthonasal routes, but substantially modulated the retronasal route: decrease (left: -41.4%, right: -44.2%) for human, and increase to the medial (29.5%) but not to lateral (-14.3%) for rat. There exist key differences between humans and rats regarding retro/orthonasal odorant transport routes, which matched well with experimental olfactory bulb activity data in literature. While humans have equivalent odorant delivery between routes, the difference in retro and orthonasal routes in rodents is substantial and changes to the transverse lamina above the nasopharynx can substantially modulate the retronasal route, but not enough to bridge the gap between the two routes.

Analyses on the influence of normal nasal morphological variations on odorant transport to the olfactory cleft

Objective Olfaction requires a combination of sensorineural components and conductive components, but conductive mechanisms have not typically received much attention. This study investigates the role of normal nasal vestibule morphological variations in ten healthy subjects on odorant flux in the olfactory cleft. Materials and methods Computed tomography images were used to create subject-specific nasal models. Each subject’s unilateral nasal cavity was classified according to its nasal vestibule shape as Standard or Notched. Inspiratory airflow simulations were performed at 15 L/min, simulating resting inspiration using computational fluid dynamics modeling. Odorant transport simulations for three odorants (limonene, 2,4-dinitrotoluene, and acetaldehyde) were then performed at concentrations of 200 ppm for limonene and acetaldehyde, and 0.2 ppm for dinitrotoluene. Olfactory cleft odorant flux was computed for each simulation. Results and discussion and conclusion Simulated results showed airflow in the olfactory cleft was greater in the Standard phenotype compared to the Notched phenotype. For Standard, median airflow was greatest in the anterior region (0.5006 L/min) and lowest in the posterior region (0.1009 L/min). Median airflow in Notched was greatest in the medial region (0.3267 L/min) and lowest in the posterior region (0.0756 L/min). Median olfactory odorant flux for acetaldehyde and limonene was greater in Standard (Acetaldehyde: Standard = 140.45 pg/cm2-s; Notched = 122.20 pg/cm2-s. Limonene: Standard = 0.67 pg/cm2-s; Notched = 0.65 pg/cm2-s). Median dinitrotoluene flux was greater in Notched (Standard = 2.86 × 10−4pg/cm2-s; Notched = 4.29 × 10−4 pg/cm2-s). The impact of nasal vestibule morphological variations on odorant flux at the olfactory cleft may have implications on individual differences in olfaction, which should be investigated further.

Alternation emerges as a multi-modal strategy for turbulent odor navigation.

Foraging mammals exhibit a familiar yet poorly characterized phenomenon, 'alternation', a pause to sniff in the air preceded by the animal rearing on its hind legs or raising its head. Rodents spontaneously alternate in the presence of airflow, suggesting that alternation serves an important role during plume-tracking. To test this hypothesis, we combine fully resolved simulations of turbulent odor transport and Bellman optimization methods for decision-making under partial observability. We show that an agent trained to minimize search time in a realistic odor plume exhibits extensive alternation together with the characteristic cast-and-surge behavior observed in insects. Alternation is linked with casting and occurs more frequently far downwind of the source, where the likelihood of detecting airborne cues is higher relative to ground cues. Casting and alternation emerge as complementary tools for effective exploration with sparse cues. A model based on marginal value theory captures the interplay between casting, surging, and alternation.

Learning to predict target location with turbulent odor plumes.

Animal behavior and neural recordings show that the brain is able to measure both the intensity and the timing of odor encounters. However, whether intensity or timing of odor detections is more informative for olfactory-driven behavior is not understood. To tackle this question, we consider the problem of locating a target using the odor it releases. We ask whether the position of a target is best predicted by measures of timing vs intensity of its odor, sampled for a short period of time. To answer this question, we feed data from accurate numerical simulations of odor transport to machine learning algorithms that learn how to connect odor to target location. We find that both intensity and timing can separately predict target location even from a distance of several meters; however, their efficacy varies with the dilution of the odor in space. Thus, organisms that use olfaction from different ranges may have to switch among different modalities. This has implications on how the brain should represent odors as the target is approached. We demonstrate simple strategies to improve accuracy and robustness of the prediction by modifying odor sampling and appropriately combining distinct measures together. To test the predictions, animal behavior and odor representation should be monitored as the animal moves relative to the target, or in virtual conditions that mimic concentrated vs dilute environments.

Surface Properties and Architectures of Male Moth Trichoid Sensilla Investigated Using Atomic Force Microscopy

The surfaces of trichoid sensilla on male moth antennae have been sculpted over evolutionary time to capture pheromone odorant molecules emitted by the females of their species and transport the molecules in milliseconds into the binding protein milieu of the sensillum lumen. The capture of pheromone molecules likely has been optimized by the topographies and spacings of the numerous ridges and pores on these sensilla. A monolayer of free lipids in the outer epicuticle covers the sensillar surfaces and must also be involved in optimal pheromone odorant capture and transport. Using electro-conductive atomic force microscopy probes, we found that electrical surface potentials of the pores, ridges and flat planar areas between ridges varied in consistent ways, suggesting that there is a heterogeneity in the distribution of surface lipid mixtures amongst these structures that could help facilitate the capture and transport of pheromone molecules down through the pores. We also performed experiments using peak force atomic force microscopy in which we heated the sensilla to determine whether there is a temperature-related change of state of some of the surface lipid exudates such as the prominent domes covering many of the pores. We found that these exudates were unaffected by heating and did not melt or change shape significantly under high heat. Additionally, we measured and compared the topographies of the trichoid sensilla of five species of moths, including the distributions, spacings, heights and diameters of ridges, pores and pore exudates.

Measuring Odor Transport of Narcotic Substances Using DART-MS

The employment of canines in matters of law enforcement is due to their heightened olfactory senses, which helps in evaluating the presence of illicit substances. However, there have been instances where canines are signaling the presence of narcotics when they are not there. This study aimed to analyze how active odorants transport from one area to another. Direct Analysis in Real-Time coupled to a high-resolution mass spectrometer (DART-MS) was used to analyze, in real-time, the volatile organic compounds (VOCs) of two narcotic substances: cocaine and methamphetamine. This study found that the transfer of VOCs from these narcotics does occur. Methyl benzoate was detected at 39.3 ± 3.2 s after exposure from 3 meters away, whereas benzaldehyde was detected at 43.3 ± 0.6 s from the same distance. The guidelines used for canine certification should be revisited to account for these results to lower or eliminate unconfirmed alerts by canines.

Olfactory cleft mucus proteome in chronic rhinosinusitis: a case-control pilot study.

Mechanisms of smell loss in chronic rhinosinusitis (CRS) are still unclear and likely multifactorial. Little attention has been given to olfactory cleft (OC) mucus proteins involved in odorant binding and metabolizing enzymes and their potential role in smell loss. Mucus from the OC was sampled from patients with CRS (n = 20) and controls (n = 10). Liquid chromatography and mass spectrometry were performed, followed by data processing so that protein groups could be identified, quantified, and compared. Hierarchical clustering and bioinformatic analysis were performed on significantly different proteins to explore for enrichment in known biologic pathways. A total of 2514 proteins were found in OC mucus from all 30 subjects. Significant differences in protein abundance were found between CRS and controls, including both CRSsNP (n = 351 proteins; log2 fold change range: -3.88 to 6.71) and CRSwNP (n = 298 proteins; log2 fold change range: -4.00 to -6.13). Significant differences were found between patients with normosmia and those with dysosmia (n = 183; log2 fold change range: -3.62 to -2.16) and across groups of interest for a number of odorant binding proteins and metabolizing enzymes. OC mucous in CRS displays a rich and abundant array of proteins, many of which have been implicated in odorant transport and metabolization in animal studies. Significant differences in the olfactory mucus proteome were seen between CRS subtypes and controls, as well as between those with normal and abnormal olfaction. Further study should confirm these findings and explore the role individual proteins play in odorant transport and metabolization. ©2020 ARSAAOA, LLC.

Antennal Proteome of the Solenopsis invicta (Hymenoptera: Formicidae): Caste Differences in Olfactory Receptors and Chemosensory Support Proteins.

Little is known about the expression pattern of odorant and pheromone transporters, receptors, and deactivation enzymes in the antennae of ants carrying out different tasks. In order to begin filling in this information gap, we compared the proteomes of the antennae of workers and males of the red fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae). Male ants do not perform any colony work, and their only activity is to leave the nest on a mating flight. Previous studies showed that male ants express fewer types of odorant receptors than workers. Thus, we expected to find large differences between male and worker antennae for expression of receptors, transporters, and deactivators of signaling chemicals. We found that the abundance of receptors was consistent with the expected caste-specific signaling complexity, but the numbers of different antenna-specific transporters and deactivating enzymes in males and workers were similar. It is possible that some of these proteins have antenna-specific functions that are unrelated to chemosensory reception. Alternatively, the similar complexity could be a vestige of ant progenitors that had more behaviorally active males. As the reduced behavior of male ants evolved, the selection process may have favored a complex repertoire of transporters and deactivating enzymes alongside a limited repertoire of odorant receptors.

Interactions Between Odorants and Glutathione Transferases in the Human Olfactory Cleft.

Xenobiotic metabolizing enzymes and other proteins, including odorant-binding proteins located in the nasal epithelium and mucus, participate in a series of processes modulating the concentration of odorants in the environment of olfactory receptors (ORs) and finely impact odor perception. These enzymes and transporters are thought to participate in odorant degradation or transport. Odorant biotransformation results in 1) changes in the odorant quantity up to their clearance and the termination of signaling and 2) the formation of new odorant stimuli (metabolites). Enzymes, such as cytochrome P450 and glutathione transferases (GSTs), have been proposed to participate in odorant clearance in insects and mammals as odorant metabolizing enzymes. This study aims to explore the function of GSTs in human olfaction. Using immunohistochemical methods, GSTs were found to be localized in human tissues surrounding the olfactory epithelium. Then, the activity of 2 members of the GST family toward odorants was measured using heterologously expressed enzymes. The interactions/reactions with odorants were further characterized using a combination of enzymatic techniques. Furthermore, the structure of the complex between human GSTA1 and the glutathione conjugate of an odorant was determined by X-ray crystallography. Our results strongly suggest the role of human GSTs in the modulation of odorant availability to ORs in the peripheral olfactory process.