Molecular vibration-sensing component in
            <i>Drosophila melanogaster</i>
            olfaction

Franco, Maria Isabel; Turin, Luca; Mershin, Andreas; Skoulakis, Efthimios M. C.

doi:10.1073/pnas.1012293108

Cited by 176 publications

(244 citation statements)

References 42 publications

(51 reference statements)

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“…Earlier claims that human subjects can distinguish odors of acetophenone isotopomers (9,35) have been shown to be untrue (14,31). Recent studies indicate that Drosophila melanogaster can distinguish acetophenone isotopomers (36,37) and that Apis mellifera L., the honey bee, can be trained to discriminate pairs of isotopomers (38). These studies differ from earlier insect studies in which isotopomer discrimination was not found.…”

Section: Significancementioning

confidence: 84%

Implausibility of the vibrational theory of olfaction

Block

Jang

Matsunami

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

115

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The vibrational theory of olfaction assumes that electron transfer occurs across odorants at the active sites of odorant receptors (ORs), serving as a sensitive measure of odorant vibrational frequencies, ultimately leading to olfactory perception. A previous study reported that human subjects differentiated hydrogen/ deuterium isotopomers (isomers with isotopic atoms) of the musk compound cyclopentadecanone as evidence supporting the theory. Here, we find no evidence for such differentiation at the molecular level. In fact, we find that the human musk-recognizing receptor, OR5AN1, identified using a heterologous OR expression system and robustly responding to cyclopentadecanone and muscone, fails to distinguish isotopomers of these compounds in vitro. Furthermore, the mouse (methylthio)methanethiol-recognizing receptor, MOR244-3, as well as other selected human and mouse ORs, responded similarly to normal, deuterated, and 13 C isotopomers of their respective ligands, paralleling our results with the musk receptor OR5AN1. These findings suggest that the proposed vibration theory does not apply to the human musk receptor OR5AN1, mouse thiol receptor MOR244-3, or other ORs examined. Also, contrary to the vibration theory predictions, muscone-d 30 lacks the 1,380-to 1,550-cm −1 IR bands claimed to be essential for musk odor. Furthermore, our theoretical analysis shows that the proposed electron transfer mechanism of the vibrational frequencies of odorants could be easily suppressed by quantum effects of nonodorant molecular vibrational modes. These and other concerns about electron transfer at ORs, together with our extensive experimental data, argue against the plausibility of the vibration theory.olfaction | isotopomers | cyclopentadecanone | muscone | electron transfer I n 1870, the British physician William Ogle wrote: "As in the eye and the ear the sensory impression is known to result not from the contact of material particles given off by the object seen or heard, but from waves or undulations of the ether or the air, one cannot but suspect that the same may be true in the remaining sense, and that the undulatory theory of smell. . . [may be] the true one" (1, 2). Of the 29 different "theories of odour" listed in the 1967 edition of The Chemical Senses (3), nine associate odor with vibrations, particularly those theories championed by Dyson (4, 5) and Wright (6-8). However, the premise that olfaction involves detection of vibrational frequencies of odorants remains highly speculative because neither the structures of the odorant receptors (ORs) nor the binding sites or the activation mechanisms triggered upon odorant binding to ORs have been established. In 1996-1997, Turin (9-12) elaborated on the undulatory theory of smell, as considered in more detail below, and suggested that a mechanism analogous to inelastic electron tunneling spectroscopy (13) may be involved, where tunneling electrons in the receptor probe the vibrational frequencies of odorants. In 2013, Gane et al. (14) In judging the plausibility...

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Section: Significancementioning

confidence: 84%

Implausibility of the vibrational theory of olfaction

Block

Jang

Matsunami

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

115

View full text Add to dashboard Cite

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“…The Markov approximation amounts to replacing the state at time s in the integrand of Eq. (26) with the state at time t, changing variables such that s → t − τ , and taking the integral to infinity:…”

Section: Appendix: Derivation Of the Master Equationmentioning

confidence: 99%

“…may be possible to distinguish the scents of some very similar odorants, for example between those that are deuterated and non-deuterated. 26,30,37 It was suggested as early as 1938 that the sensing of vibrational spectra of molecules [38][39][40] -later proposed to occur via electron transfer 21,22 -could play an important role in olfaction, supplementing (rather than replacing) the existing lockand-key model. Recent work, focussing on constructing and exploring model systems that capture the important physical processes, 24,27 has shown that this is indeed a viable proposition.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, obtaining a deeper understanding of olfaction, the mechanism for which is still being actively debated, [21][22][23][24][25][26][27][28][29][30] is an important problem in its own right for both fundamental science and industry. [31][32][33][34][35] The prevailing theory, known as the lock-and-key model, explains how the odorant size and shape can provide discrimination in the receptor.…”

Section: Introductionmentioning

confidence: 99%

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Dissipation enhanced vibrational sensing in an olfactory molecular switch

Chęcińska

Pollock

Heaney

et al. 2015

The Journal of Chemical Physics

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Motivated by a proposed olfactory mechanism based on a vibrationally-activated molecular switch, we study electron transport within a donor-acceptor pair that is coupled to a vibrational mode and embedded in a surrounding environment. We derive a polaron master equation with which we study the dynamics of both the electronic and vibrational degrees of freedom beyond previously employed semiclassical (MarcusJortner) rate analyses. We show: (i) that in the absence of explicit dissipation of the vibrational mode, the semiclassical approach is generally unable to capture the dynamics predicted by our master equation due to both its assumption of one-way (exponential) electron transfer from donor to acceptor and its neglect of the spectral details of the environment; (ii) that by additionally allowing strong dissipation to act on the odorant vibrational mode we can recover exponential electron transfer, though typically at a rate that differs from that given by the Marcus-Jortner expression; (iii) that the ability of the molecular switch to discriminate between the presence and absence of the odorant, and its sensitivity to the odorant vibrational frequency, are enhanced significantly in this strong dissipation regime, when compared to the case without mode dissipation; and (iv) that details of the environment absent from previous Marcus-Jortner analyses can also dramatically alter the sensitivity of the molecular switch, in particular allowing its frequency resolution to be improved. Our results thus demonstrate the constructive role dissipation can play in facilitating sensitive and selective operation in molecular switch devices, as well as the inadequacy of semiclassical rate equations in analysing such behaviour over a wide range of parameters.

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“…This has even been extended to the rather extreme proposal that our sense of olfaction is based on vibrational modes, 88 which is clearly really problematic (see, e.g., Ref. 89), and will therefore not be examined here.…”

Section: Mode Coupling Dynamical Effects and Compressionmentioning

confidence: 99%

Enhancement of the droplet nucleation in a dense supersaturated Lennard-Jones vapor

Zhukhovitskii

2016

The Journal of Chemical Physics

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The vapor–liquid nucleation in a dense Lennard-Jones system is studied analytically and numerically. A solution of the nucleation kinetic equations, which includes the elementary processes of condensation/evaporation involving the lightest clusters, is obtained, and the nucleation rate is calculated. Based on the equation of state for the cluster vapor, the pre-exponential factor is obtained. The latter diverges as a spinodal is reached, which results in the nucleation enhancement. The work of critical cluster formation is calculated using the previously developed two-parameter model (TPM) of small clusters. A simple expression for the nucleation rate is deduced and it is shown that the work of cluster formation is reduced for a dense vapor. This results in the nucleation enhancement as well. To verify the TPM, a simulation is performed that mimics a steady-state nucleation experiments in the thermal diffusion cloud chamber. The nucleating vapor with and without a carrier gas is simulated using two different thermostats for the monomers and clusters. The TPM proves to match the simulation results of this work and of other studies.

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Molecular vibration-sensing component in Drosophila melanogaster olfaction

Cited by 176 publications

References 42 publications

Implausibility of the vibrational theory of olfaction

Implausibility of the vibrational theory of olfaction

Dissipation enhanced vibrational sensing in an olfactory molecular switch

Enhancement of the droplet nucleation in a dense supersaturated Lennard-Jones vapor

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