Transport competition and selectivity in a biomimetic nanofluidic system Biological

Envoyé par fabien.montel 
Transport competition and selectivity in a biomimetic nanofluidic system Biological
jeudi 30 septembre 2021 11:03:09
Laboratory name: Laboratoire de Physique, ENS de Lyon
CNRS identification code: UMR 5672
Supervisor: Fabien Montel
e-mail: Fabien.montel@ens
Phone number: +33 (0)4 26 23 38 23
Web page: [url=http://perso.ens]http://perso.ens[/url]

[b]Transport competition and selectivity in a biomimetic nanofluidic system[/b]
Biological pores are essential actors in cell function. For example, ion channels are responsible for the transmission of neuronal information while the nuclear pore has an essential role in the regulation of gene expression [1,2]. One of their most remarkable properties is the selectivity of these nanofluidic channels and their ability to select from the complex mixture that is the cellular medium only the molecule that must be trans ported and the direction of this transport. In the case of pores involved in the transport of macromolecules such as the nuclear pore which regulates exchanges between the nucleus and the cytoplasm, it has been shown that selectively transported species carry a peptide signal
(NLS, nuclear localization signal) which induces a higher affinity for a transporter and ultimately the central channel of the nuclear pore [1].
The wide variety of proteins with significant affinity for the nuclear pore raises the question of the robustness of this mechanism. For example, how sensitive is the phenomenon to changes in the concentration of one of the competitors on the flow of a par ticular species? Surprisingly, recent theoretical work has shown that a molecule can exhibit a higher translocation rate in the presence of competing molecules and that there is a flux optimum for a particular affinity [3,4].
In this project we propose to use a nuclear pore mimetic approach to measure the effect of multi species competition at the pore entrance on the selectivity and flux of molecules through the pore. We will use artificial functionalized nanoporous membranes to reproduce the essential ele ments of this phenomenon. We will then measure the link between affinity for the nanopore and the ability to maintain a high flux of material through the pore. The measurement of the translocation frequency will be performed at the single molecule scale by Zero Mode waveguide, a highly parallelized optical near field method devel oped in the team [5,6]. Our results will allow the construction of a quantitative and detailed representation of the impact of competition between several actors at the pore entrance on the translocation energy landscape across the nanopore.

References :
1. Wente SR, Rout MP. Cold Spring Harb Perspect Biol. 2010 Oct;2(10):a000562.
2. Selles J , Penrad Mobayed M, Guillaume C, Fuger A, Auvray L, Faklaris O, Montel F. Scientific Report s 7 (14732) NOV 7 2017
3. Zilman A, Di Talia S, Jovanovic Talisman T, Chait BT, Rout MP, Magnasco MO. PLoS Comput Biol. 2010 Jun 10;6(6):e1000804.
4. Zilman A, Di Talia S, Chait BT, Rout MP, Magnasco MO. PLoS Comput Biol. 2007 Jul;3(7):e125.
5. Auger T, Mathé J, Viasnoff V, Charron G, Di Meglio JM, Auvray L, Montel F. Phys Rev Lett. 2014 Jul 11;113(2):028302.
6. Auger T, Bourhis E, Donnez J, Durnez A, Di Meglio JM, Auvray L, Montel F, Yates J, Gierak J. Microelectronic Engineering 187, 90 94