Chaotic Dynamics of Inner Ear Hair Cells

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Hearing loss affects about 30 million patients in United States. Since loss or damage to hair cells of the inner ear can lead to profound deafness, it is important to understand the mechanisms of their proper functioning, as a prerequisite to progress in future clinical treatments. This study is aimed at elucidating how this biological sensor works, knowing which can hence aid in future studies of how it fails. Nonlinear processes and active amplification have been shown to be key to the extreme sensitivity of audition. While many studies have explored the various potential mechanisms of amplification, the role of either deterministic or stochastic noise has received comparatively little attention. This project is hence complementary to most of the work currently performed in the field, and could provide some of the missing information on how the auditory and vestibular systems achieve the sensitivity in the presence of fluctuations. This approach requires a combination of experimental and theoretical studies to address this long-open problem. The PI proposes to combine educational efforts with the research program, to teach undergraduate students topics of relevance for the physics of living systems. Building on prior courses, she will introduce a new class that will expose students to the applications of statistical mechanics and nonlinear dynamics to a broad range of open questions in biology. She also proposes to launch new workshops, aimed at bringing together scientists from different fields of theoretical physics and biologists studying the auditory system.Hair cells of the inner ear are the biological sensors that detect displacements induced by air-borne or ground-borne vibrations and transduce them into electrical signals. Their responsiveness is crucially dependent on an active process that amplifies oscillations induced by the incoming sound. One of the signatures of the active process, hair cell bundles, have been shown to exhibit limit cycle oscillations, spontaneous motion in the absence of any input. The PI hypothesizes that the innate motility exhibits chaotic behavior, and proposes to test how chaos impacts the sensitivity of detection. Long recordings of hair cells of the bullfrog sacculus will be obtained in vitro, and analytic tools from dynamic systems theory will be applied to extract the Lyapunov exponents, construct Poincare maps, and estimate the Kolmogorov entropy characterizing the motion. The hair cells will then be subject to mechanical stimulation of varying intensity and duration, to observe how the chaotic regime is impacted by external signals. Pharmacological and electrical manipulation will also be used to poise the cells in different dynamical states. The goal is to determine whether and how this biological system harnesses chaos to enhance its detection sensitivity. Estimates of the passive mechanical properties of a hair bundle indicate that its thermal fluctuations in water should be almost an order of magnitude higher than the detection threshold. The PI proposes to study the role of noise in the response of hair bundles, and specifically whether it can aid in the detection of applied signals. She aims to explain how sensitive mechanical detection could be performed in a system immersed in an aqueous medium, maintained at room or higher temperatures, and hence subject to significant thermal fluctuations. The study will provide insight into the fundamental mechanism of hearing, as well as providing a general model for the role of chaos in the sensitivity of detection by an active system.This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Neural Cluster in the Integrative Organismal Systems Division.