Nonlinear amplification by active sensory hair bundles

The human sense of hearing is characterized by its exquisite sensitivity, sharp frequency selectivity, and wide dynamic range. These features depend on an active process that in the inner ear boosts vibrations evoked by auditory stimuli. Spontaneous otoacoustic emissions constitute a demonstrative manifestation of this physiologically vulnerable mechanism. In the cochlea, sensory hair bundles transduce sound-induced vibrations into neural signals. Hair bundles can power mechanical movements of their tip, oscillate spontaneously, and operate as tuned nonlinear amplifiers of weak periodic stimuli. Active hair-bundle motility constitutes a promising candidate with respect to the biophysical implementation of the active process underlying human hearing. The responsiveness of isolated hair bundles, however, is seriously hampered by intrinsic fluctuations. In this thesis, we present theoretical and experimental results concerning the noise-imposed limitations of nonlinear amplification by active sensory hair bundles. We analyze the effect of noise within the framework of a stochastic description of hair-bundle dynamics and relate our findings to generic aspects of the stochastic dynamics of oscillatory systems. Hair bundles in vivo are often elastically coupled by overlying gelatinous membranes. In addition to theoretical results concerning the dynamics of elastically coupled hair bundles, we report on an experimental study. We have interfaced dynamic force clamp performed on a hair bundle from the sacculus of the bullfrog with real-time stochastic simulations of hair-bundle dynamics. By means of this setup, we could couple a hair bundle to two virtual neighbors, called cyber clones. Our theoretical and experimental work shows that elastic coupling leads to an effective noise reduction. Coupled hair bundles exhibit an increased coherence of spontaneous oscillations and an enhanced amplification gain. We therefore argue that elastic coupling by overlying membranes constitutes a morphological specialization for reducing the detrimental effect of intrinsic fluctuations

Voltage Oscillations and Response Dynamics in a Model of Sensory Hair Cells

We used a Hodgkin-Huxley type model of the basolateral ionic currents of bullfrog sacculus to study genesis of spontaneous voltage oscillation patterns and how the spontaneous oscillations shape the response of the hair cell to external mechanical stimuli

Spontaneous Voltage Oscillations and Response Dynamics of a Hodgkin-Huxley Type Model of Sensory Hair Cells

We employ a Hodgkin-Huxley-type model of basolateral ionic currents in bullfrog saccular hair cells for studying the genesis of spontaneous voltage oscillations and their role in shaping the response of the hair cell to external mechanical stimuli. Consistent with recent experimental reports, we find that the spontaneous dynamics of the model can be categorized using conductance parameters of calciumactivated potassium, inward rectifier potassium, and mechano-electrical transduction (MET) ionic currents. The model is demonstrated for exhibiting a broad spectrumof autonomous rhythmic activity, including periodic and quasi-periodic oscillations with two independent frequencies as well as various regular and chaotic bursting patterns. Complex patterns of spontaneous oscillations in the model emerge at small values of the conductance of Ca2+-activated potassium currents. These patterns are significantly affected by thermal fluctuations of the MET current. We show that selfsustained regular voltage oscillations lead to enhanced and sharply tuned sensitivity of the hair cell to weak mechanical periodic stimuli. While regimes of chaotic oscillations are argued to result in poor tuning to sinusoidal driving, chaotically oscillating cells do provide a high sensitivity to low-frequency variations of external stimuli

Nonlinear amplification by active sensory hair bundles

The human sense of hearing is characterized by its exquisite sensitivity, sharp frequency selectivity, and wide dynamic range. These features depend on an active process that in the inner ear boosts vibrations evoked by auditory stimuli. Spontaneous otoacoustic emissions constitute a demonstrative manifestation of this physiologically vulnerable mechanism. In the cochlea, sensory hair bundles transduce sound-induced vibrations into neural signals. Hair bundles can power mechanical movements of their tip, oscillate spontaneously, and operate as tuned nonlinear amplifiers of weak periodic stimuli. Active hair-bundle motility constitutes a promising candidate with respect to the biophysical implementation of the active process underlying human hearing. The responsiveness of isolated hair bundles, however, is seriously hampered by intrinsic fluctuations. In this thesis, we present theoretical and experimental results concerning the noise-imposed limitations of nonlinear amplification by active sensory hair bundles. We analyze the effect of noise within the framework of a stochastic description of hair-bundle dynamics and relate our findings to generic aspects of the stochastic dynamics of oscillatory systems. Hair bundles in vivo are often elastically coupled by overlying gelatinous membranes. In addition to theoretical results concerning the dynamics of elastically coupled hair bundles, we report on an experimental study. We have interfaced dynamic force clamp performed on a hair bundle from the sacculus of the bullfrog with real-time stochastic simulations of hair-bundle dynamics. By means of this setup, we could couple a hair bundle to two virtual neighbors, called cyber clones. Our theoretical and experimental work shows that elastic coupling leads to an effective noise reduction. Coupled hair bundles exhibit an increased coherence of spontaneous oscillations and an enhanced amplification gain. We therefore argue that elastic coupling by overlying membranes constitutes a morphological specialization for reducing the detrimental effect of intrinsic fluctuations

Improving silica compound processing:Optimization of the mixing equipment

Different mixers and mixer adjustments were tested in laboratory for the efficiency of the silanization process. New silanes were developed with the aim to reduce the scorch risk during mixing and silanization. The Payne effect was used to quantify the amount of filler-filler interaction in a rubber compound. It is observed that air injection has a positive effect on the silanization efficiency without influencing the overall properties of the material.</p

In vivo force application reveals a fast tissue softening and external friction increase during early embryogenesis

During development, cell-generated forces induce tissue-scale deformations to shape the organism [1,2]. The pattern and extent of these deformations depend not solely on the temporal and spatial profile of the generated force fields but also on the mechanical properties of the tissues that the forces act on. It is thus conceivable that, much like the cell-generated forces, the mechanical properties of tissues are modulated during development in order to drive morphogenesis toward specific developmental endpoints. Although many approaches have recently emerged to assess effective mechanical parameters of tissues [3-8], they could not quantitatively relate spatially localized force induction to tissue-scale deformations in vivo. Here, we present a method that overcomes this limitation. Our approach is based on the application of controlled forces on a single microparticle embedded in an individual cell of an embryo. Combining measurements of bead displacement with the analysis of induced deformation fields in a continuum mechanics framework, we quantify material properties of the tissue and follow their changes over time. In particular, we uncover a rapid change in tissue response occurring during Drosophila cellularization, resulting from a softening of the blastoderm and an increase of external friction. We find that the microtubule cytoskeleton is a major contributor to epithelial mechanics at this stage. We identify developmentally controlled modulations in perivitelline spacing that can account for the changes in friction. Overall, our method allows for the measurement of key mechanical parameters governing tissue-scale deformations and flows occurring during morphogenesis.The research leading to these results has received funding from the Spanish Ministry of Economy and Competitiveness (MEIC) to the EMBL partnership, Plan Nacional, BFU2010-16546 and BFU2015-68754, and “Centro de Excelencia Severo Ochoa 2013–2017,” SEV-2012-0208. We acknowledge the support of the CERCA Programme/Generalitat de Catalunya. G.S. is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001317), UK Medical Research Council (FC001317), and Wellcome Trust (FC001317