A5009724024- Hearing, Cochlea, Tinnitus, Genetics
- Hearing Loss and Rehabilitation
- Acoustic Wave Phenomena Research
- RNA and protein synthesis mechanisms
- Vestibular and auditory disorders
- Advanced Sensor and Energy Harvesting Materials
- Ear Surgery and Otitis Media
- RNA regulation and disease
- Force Microscopy Techniques and Applications
- Analytical Chemistry and Sensors
- Ion Channels and Receptors
- Mechanical and Optical Resonators
- Micro and Nano Robotics
- Surface Modification and Superhydrophobicity
- Cardiovascular and Diving-Related Complications
- Biomimetic flight and propulsion mechanisms
- Textile materials and evaluations
- CRISPR and Genetic Engineering
- Neural dynamics and brain function
- Neural Networks and Applications
- Cellular Mechanics and Interactions
- Connexins and lens biology
- Animal Vocal Communication and Behavior
- Bat Biology and Ecology Studies
- Marine animal studies overview
Harvard University
2006-2024
Howard Hughes Medical Institute
2006-2018
Stanford University
2011
Boston University
2003-2007
Massachusetts Institute of Technology
2007
Hereditary hearing loss often results from mutation of genes expressed by cochlear hair cells. Gene addition using AAV vectors has shown some efficacy in mouse models, but clinical application requires two additional advances. First, new capsids must mediate efficient transgene expression both inner and outer cells the cochlea. Second, to have best chance translation, these also transduce non-human primates. Here, we show that an AAV9 capsid variant, PHP.B, produces a GFP reporter neonatal...
We report the development of a new class miniature all-polymer flow sensors that closely mimic intricate morphology mechanosensory ciliary bundles in biological hair cells. An artificial bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The nature single link confirmed X-ray diffraction (XRD) Fourier transform infrared spectroscopy (FTIR). Rheology...
When the tip of a hair bundle is deflected by sensory stimulus, stereocilia pivot as unit, producing shearing displacement between adjacent tips. It not clear how can stick together laterally but still shear. We used dissociated cells from bullfrog saccule and high-speed video imaging to characterize this sliding adhesion. Movement individual was proportional height, indicating that at their basal insertion points. All moved approximately same angular deflection, motion observed 1, 20, 700...
The transmembrane (TM) channel-like 1 (TMC1) and TMC2 proteins play a central role in auditory transduction, forming ion channels that convert sound into electrical signals. However, the molecular mechanism of their gating remains unknown. Here, using predicted structural models as guide, we probed effects 12 mutations on mechanical transduction currents native hair cells Tmc1/2 -null mice expressing virally introduced TMC1 variants. Whole-cell electrophysiological recordings revealed within...
Hair cells of the inner ear are mechanoreceptors for hearing and balance, proteins highly enriched in hair may have specific roles development maintenance mechanotransduction apparatus. We identified XIRP2/mXinβ as an protein likely to be essential cells. found that different isoforms this expressed differentially located: short splice forms (also called XEPLIN) targeted more stereocilia, whereas two long containing a XIN-repeat domain both stereocilia cuticular plates. Mice lacking Xirp2...
We present the fabrication of an artificial MEMS hair bundle sensor designed to approximate structural and functional principles flow-sensing bundles found in fish neuromast cells. The consists micro-pillars graded height connected with piezoelectric nanofiber "tip-links" encapsulated by a hydrogel cupula-like structure. Fluid drag force actuates cupula deflects micro-pillar bundle, stretching nanofibers generating electric charges. These biomimetic sensors achieve ultrahigh sensitivity...
The forces felt by different transduction channels in a bundle depend critically on how well stereocilia remain cohesive during deflection. In the bullfrog saccule, sliding adhesion mediated horizontal top connectors (HTC) confers coherent motion to hair cell and parallel gating all channels. cochlear inner outer cells (IHCs OHCs), mature complement of HTC is established postnatal day 12; they extend between adjacent both rows columns. Contrary our expectation that cohesion should be robust...
The forces felt by different transduction channels in a bundle depend critically on how well stereocilia remain cohesive during deflection. In the bullfrog saccule, sliding adhesion mediated horizontal top connectors (HTC) confers coherent motion to hair cell and parallel gating all channels. cochlear inner outer cells (IHCs OHCs), mature complement of HTC is established postnatal day 12; they extend between adjacent both rows columns. Contrary our expectation that cohesion should be robust...
Abstract Mutations in the GJB2 gene cause most common form of human hereditary hearing loss, known as DFNB1. is expressed two cell groups cochlea—epithelial cells organ Corti and fibrocytes inner sulcus lateral wall—but not by sensory hair or neurons. Attempts to treat mouse models DFNB1 with AAV vectors mediating nonspecific Gjb2 expression have substantially restored function, perhaps because inappropriate neurons could compromise their electrical activity. Here, we used genomic chromatin...
We present an innovative design for a flexible probe to study mechanisms of biological force sensing and generation in the piconewton micronewton range. Made polydimethylsiloxane (PDMS) employing novel ring-spring section with adjustable size, device works both as sensor actuator by precise calibration its tunable stiffness optical measurement ring deformation. In addition, tip geometry can be properly shaped fit anatomical profile sensory receptor interest reproduce vivo stimulation....
This paper presents the design and analysis of an innovative PDMS probe for investigating mechanotransduction force generation by mechanosensory cells organs. The low Young's modulus together with a novel ring-spring allow easily tunable stiffness 1-100 mN/m or larger. limits fluid drag allows settling times 200 μs less depending on compliance probe. Moreover, custom-tailored tip geometry this device good coupling to variety sensory structures. can be used as sensor actuator using...
The study of mechanotransduction in cochlear hair cells requires stimulus methods that mimic the in-vivo stimulation. We have developed a new mechanical probe to better physiological delivered through overlying tectorial membrane. combine these probes with electroporation contribution different components transduction apparatus.
When the tip of a hair bundle is deflected, stereocilia pivot as unit, producing shearing displacement between adjacent tips. It not clear how can stick together laterally but still shear. We used dissociated cells from bullfrog saccule and high‐speed video imaging to characterize this sliding adhesion. Movement individual was proportional height, indicating that at their basal insertion points. All moved by approximately same angular deflection, motion observed 1, 20 700 Hz stimulus...
A discussion moderated by the authors on topic “Hair Cells: Bundles, Tuning, Transduction” was held 17 July 2011 at 11th International Mechanics of Hearing Workshop in Williamstown, Massachusetts. The paper provides an edited transcript session.
Electrically-evoked outer-hair-cell-driven micromechanical motions within the organ of Corti were visualized and quantified using a video stroboscopy system. The resulting radial exhibited phase transitions along direction, characteristic system that can exhibit multiple modes vibration. We argue interaction these would shape input to inner hair cell bundles auditory-nerve response patterns.
The mammalian cochlea contains two types of sensory cells, inner hair cells (IHCs) and outer (OHCs). IHCs provide the vast majority synaptic input to auditory nerve while OHCs express a unique motor protein, prestin, appear participate in an electromechanical feedback loop that amplifies motion organ Corti (OC). To study this amplification process we have employed stroboscopic video microscopy quantify various elements OC. Extracellular electrical stimulation was used excite OHC motility...
Abstract The trans m embrane c hannel-like (TMC) 1 and 2 proteins play a central role in auditory transduction, forming ion channels that convert sound into electrical signals. However, the molecular mechanism of their gating remains unknown. Here, using predicted structural models as guide, we probed effects twelve mutations on mechanical transduction currents native hair cells Tmc1/2 -null mice expressing virally introduced TMC1 variants. Whole-cell electrophysiological recordings revealed...