Ion channels are key regulators of mitochondrial functions. The transport of ions across the mitochondrial membrane is essential in maintaining energy production for the cell. The core aim of this project is in the development of novel nonequilibrium simulation methods to unravel the underlying molecular mechanism of how focused ultrasound influences ion channels activity and leads to regulation of mitochondrial function/dysfunction. Simulated ionic currents will offer an unprecedented view on the ion permeation process, protein conformational changes and lipid rearrangements with the timescale extending from picoseconds to microseconds.

B. O’Rourke. Mitochondrial ion channels. Annu. Rev. Physiol. 2007, 69, 19

Testai, S. Rapposelli, A. Martelli, M. C. Breschi  and V. Calderone. (2015). Mitochondrial potassium channels as pharmacological target for cardioprotective drugs. Med. Res. Rev. 2015, 35, 520

R. J. Stephens, C. A. Torbit, D. G. Groth, J. C. Taenzer and P. D. Edmonds. Mitochondrial Changes Resulting from Ultrasound Irradiation. Ultrasound in Medicine 1978, 591.

V. A. Selivanov, V. P. Zinchenko and  A. P. Sarvazian. Mechanism of low intensity ultrasound effect on mitochondria. Biofizika 1982, 27, 653

K. Lin, Z. Lin, Y. Li, Y. Zheng and D. Zhang. Ultrasound-induced reactive oxygen species generation and mitochondria-specific damage by sonodynamic agent/metal ion-doped mesoporous silica. RSC Adv. 2019, 9, 39924

V. H. Man, P. Derreumaux, P. H. Nguyen. Nonequilibrium all-atom molecular dynamics simulation of the ultrasound induced bubble vibration and application to dissociate amyloid fibrils. J. Chem. Phys. 2016, 145, 174113

V. H. Man, P. M. Truong, M. S. Li, J. Wang, V. O. Nguyen-Thi, P. Derreumaux and P.H. Nguyen. Molecular mechanism of the cell membrane pore formation induced by bubble stable cavitation. J. Phys. Chem. B. 2019, 123, 71.

V. H. Man, M.S. Li, J. Wang, P. Derreumaux and P.H. Nguyen. Interaction mechanism between the focused ultrasound and lipid membrane at the molecular level. J. Chem. Phys. 2019, 150, 215101.

V. H. Man, M.S. Li, J. Wang, P. Derreumaux, T. T. Nguyen, S. Nangia and P.H. Nguyen. Molecular mechanism of ultrasound interaction with a blood brain barrier model. Chem. Phys. 2020, 153, 045104.

V. H. Man, M.S. Li, J. Wang, P. Derreumaux and P.H. Nguyen. Molecular Mechanism of Ultrasound Induced  Structural Defects in Liposomes: a Nonequilibrium Molecular Dynamics Simulation Study. Langmuir 2021, 37, 7945

For more information on host lab, click here:

http://www-lbt.ibpc.fr/cofund-projects