The sense of smell is a significant physiological advantage exploited by many organisms including humans and it may be adversely affected by illnesses, such as caused by viral infections as exemplified recently by the COVID-19 disease. Yet, the mechanism by which organisms are able to detect and differentiate between thousands of different odors, which are transmitted by small chemical molecules named odorants, is currently not known. There are two competing hypotheses regarding the first steps in the complex odorant detection reaction, which is carried out by dedicated receptors in specialized olfactory cells. The first hypothesis assumes that odors are encoded in the shape of odorant molecules and their shapes are identified by receptors’ interior cavities into which odorants fit similar to how a correct key fits into a lock. The second hypothesis considers that smell is related to odorant molecules vibrating at specific frequencies and these molecular vibrations are probed and detected by receptors through a complex, quantum mechanics-based electron tunneling mechanism. This project aims at exploring the vibrational hypothesis of odor detection by exploiting cutting edge quantum-mechanics based experimental measurements and computational modeling of the interaction between vibrating odorants and tunneling electrons in the absence and presence of olfactory receptors. Quantum mechanics-based modeling of the interaction between vibrating odorants and electrons will accompany experiments and will clarify the experimental results. This exploratory research will significantly contribute to an understanding of one of the most fundamental biological sensing mechanisms and may help in future developments of artificial “noses†with near single-molecule detection sensitivity. The project will provide ample opportunities for training of postdoctoral, PhD and undergraduate students in multidisciplinary fields involving quantum chemistry, nanotechnology and bioengineering.
This research will contribute to the understanding of one of the frontiers of quantum effects in biology with a set of experimental and theoretical investigations aimed at providing evidence confirming or rejecting the model of Quantum Mechanical-based olfaction mechanism. This model, known as the “Vibrational Theory of Olfaction, VTO†relates molecules’ scent to their vibrational spectra and postulates that odor recognition involves quantum mechanical inelastic tunneling of electrons through the odorant-bound receptor. However, this mechanism has remained unproven and controversial. This project will use scanning tunneling microscopy (STM) to measure the tunneling current in the absence and presence of odorant molecules in the nano-junction as well as the dependence of the tunneling current on the bias voltage (tunneling spectroscopy). In the second phase of the project, Odorants will be reconstituted in lipid nanodiscs that will be attached to a conductive surface for STM measurements aimed at capturing inelastic electron tunneling. In addition, computational studies of the inelastic tunneling in the presence of odorant molecules in the tunneling junctions will be used to model the experimental conditions and to provide microscopic understanding of electron tunneling. The inelastic effects calculated will be used to compare with experimental data and provide insight on the roles the vibrational modes. Inelastic electron tunneling through odorant molecules will be studied with state-of-the-art quantum mechanical formalism. This project is supported by the Molecular Biophysics cluster of the Molecular and Cellular Biosciences Division in the Directorate for Biological Sciences
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
