Fruit Flies and the Smell Sense: How a Molecule's Vibration Can Change Its Smell

Uploaded by BeckmanInstitute on 17.09.2012

My name is Ilia Solov'yov, and I work at the Beckman Institute
at the University of Illinois at Urbana-Champaign.
One of the projects that I am really interested in
is trying to understand the biophysical mechanism of the smell sense.
In the nose of a human being or an animal, there are thousands of different receptors
which detect small molecules which cause the sense of smell.
There are different types of olfactory receptors, which are tuned for different odorants.
And the mechanism for how this biological function
is triggered, is still not completely understood.
And this is what we are trying to do here at the Beckman Institute.
There are two ideas of how the sense of smell works.
The first idea is the so-called shape mechanism; where
in the nose, all the receptor cavities have a little bit different shape.
So, they could accommodate only very specific molecules.
For example, if one talks about a ring-shaped molecule,
it is unlikely to bind with a receptor which is supposed to detect linear
shaped molecules.
So the shape is important to accommodate a specific
odorant molecule in a particular receptor.
But, there is still the question, 'What happens after this binding has occurred?'
In this respect, there is another theory.
The other theory is a so-called vibrationally assisted mechanism of smell.
The way how it works is: once an odorant molecule enters the receptor, it triggers a
quantum mechanical process of electron transfer through the receptor.
This idea is actually very simple. So, imagine an olfactory receptor without
an odorant molecule inside. It is believed that the receptor has two sides:
the so-called donor side, and the acceptor side.
The donor side initially has an electron, which tries hard to get to the acceptor side.
And this transfer is hardly possible without the presence of external molecules because
of the energetics of the receptor.
But once an odorant molecule is bound to the receptor,
it vibrates at certain characteristic frequencies.
And this vibration assists the electron tunneling from the donor to the acceptor.
But, even if the shape of two molecules is identical,
sometimes their constituent atoms may be different.
Here, you can see two odorant molecules. And, as you
can see, they have absolutely the same shape.
But, because the second molecule, shown here, contains
deuterium, compared to the hydrogen here,
the vibrational frequency for this molecule is lower.
So, even if the shape of the molecules is the same,
the chemical reactions would be different.
So, we believe that there is a complicated interaction of these two factors
and both them matter and are important for olfaction.
An example of this was performed by a group of scientists in Greece,
where fruit flies were tested in a so-called 'T-Maze'.
A T-maze is nothing more than just a glass tube,
which is filled with fruit flies.
And at both ends of the glass tube, one can put two distinctly different odorants.
And fruit flies choose one odorant in favor of the other one by spending more time in
glass tube, closer to the more preferential odorant.
But, at the next step, the scientists in Greece took one of the odorants out
and they modified its chemical structure by replacing
all of the hydrogen atoms with heavier deuterium.
This modification does not change the shape of the odorant molecules,
but it definitely changes the vibrational frequencies.
Because deuterium is heavier, so the molecules with deuterium vibrate with a different frequency.
And when they performed the experiment with deuterated odorant, and looked at
the distribution of the fruit flies in this T-maze,
they didn't see any preference in the either
the deuterated odorant or the non-modified odorant
from the first experiment.
So this clearly demonstrates that vibrational frequencies are
somehow related to the smell sense; at least in fruit flies.
The Greek paper is an experimental paper, so it shows a clear experiment.
But it does not go into details of the mechanism.
In our paper, we are really interested in understanding the mechanism behind this sense.
We considered the same odorants as the scientists from Greece did.
And then we have calculated the vibrational frequencies for these molecules, and demonstrated
that, for a particular vibration mode, there is a very similar electron tunneling
rate through the olfactory receptors; which we indirectly could link with the
main conclusion of the Greek scientists.
Earlier papers, that suggested this mechanism of vibrationally assisted olfaction,
they were more focused on the physical aspects of the problem.
So, what we tried to do is, we tried to see how this mechanism can be realized
in a real biological environment and biological system.
So, we looked carefully at the theory and tried
to establish the range of biophysical
parameters that a receptors, and also an odorant molecule, should have in order
for the mechanism to function.
So, this is definitely a new step.
And so I think probably this is the most important achievement in our paper.