Date : 11/06/10

Internship proposal for : Master 2

Laboratory

Physico-Chimie Curie
UMR 168 CNRS, Institut Curie, UPMC
26, rue d'Ulm 75005 Paris
Director : Jean-François Jaanny
Website : http://www.curie.fr/recherche/themes/detail_equipe.cfm/lang/_gb/id_equipe/323.htm
Main discipline : Molecular biology, Biophysics

Supervisor

Pascal Martin
email : This e-mail address is being protected from spam bots, you need JavaScript enabled to view it
phone : +33 156246748

Subjects / Tools-Methodologies

1 : cell mechanics/microscopy, micro needles, optical tweezers
2 : electrophysiology/patch clamp, drug application (iotophoresis)
3 : non-equilibrium physics of dynamical systems/numerical simulations

Summary of lab's interests

Our research at the interface between physics and biology aims at shedding light on the active mechano-sensory process that shapes the sensation of sounds at the periphery of the auditory system. Our approach combines micromanipulations of single hair cells, the recepor cells of the inner ear, and theoretical descriptions of mechano-electrical transduction by the hair cell. We are particularly interested in the hair cell's ability to power active movements of its mechanical antenna, the hair bundle. We also study the properties of molecular motors assemblies in simple biomimetic systems at the molecular level. Together we develop an approach at both cellular and molecular levels to better understand,in the context of hearing, the dynamical behavior of active mechanical structures in response to frequency-dependent external forces.

Summary of project

In vertebrates, hearing and the sense of balance are initiated in the inner ear by specialized mechano-sensory cells, the hair cells. Hair cells mediate transduction of sound-pressure waves (hearing) or head accelerations (balance) into electrical signals that then propagate along nervous pathways to the brain. Hair cells are each endowed with a mechano-sensory organelle, the hair bundle, that projects from the cell's apical surface into the surrounding fluid. Our experiments with hair cells from a low-frequency organ, the bullfrog\'s sacculus, demonstrate that this mechano-sensory antenna behaves as a sort of micro-muscle that can mobilize biochemical energy to oscillate spontaneously at 5-100 Hz. The hair cell can harness spontaneous hair-bundle oscillations to amplify its responsiveness to sinusoidal stimuli. This hair-bundle amplifier offers double benefit for auditory detection: it enlarges the range of sound intensities that can be heard by amplifying only the weakest sounds and sharpens frequency selectivity by filtering the input to the hair cell. The ability of the hair-bundle amplifier to operate in the mammalian cochlea, where characteristic frequencies of hair-cell sensitivity can achieve tens of kilohertz, has remained elusive. We propose to develop a preparation of the rat cochlea to study the active mechanical properties of the hair bundle along the tonotopic (frequency) axis of this auditory organ. In particular, using flexible micro-needle or optical tweezers to apply force to a single hair bundle, we will characterize the bundleís force-displacement relation and seek an unstable region of negative stiffness, for which there is already some evidence in the literature (Kennedy et al (2005) Nature 433:880). By changing ionic conditions (calcium), we expect the hair bundle to exhibit an oscillatory instability. We will also characterize the frequency dependence of the hair-bundle response to sinusoidal forces.