Individual Hair Research Articles

The origin and formation of hair on external valve surfaces of the tropical marine mussel Modiolus traillii (Reeve, 1857)

Direct observations using digital videography in an aquarium showed that hairs on the valve surfaces of Modiolus traillii are not periostracal in origin, as often assumed for similar features in other mussels, but are secreted and planted individually by the foot, so they are correctly termed ‘byssal hairs’. Deposition of byssal hair occurred most frequently just after dark, and the time taken to form a strand of serrated hair varied between slightly more than 1 min to almost 10 min, with a mean time of 4.4 min. We observed one individual deposit a total of 11 hairs in 3.5 h. The formation of some 25 hairs were successfully observed on video for six individuals, and about 3,000 individual hairs from 12 mussels were measured in relation to their position, size and density. While hairs varied considerably in length and width, they are consistently flattened, with one edge bearing serrations and the other edge being smooth. Long hair required more time to form compared with shorter hair, and longer hair was deposited farther away from the byssal gape towards the posterior end of the valves. However, a higher density of short hair was laid around the byssal gape. Smaller mussels tended to have an overall higher density of hair compared with larger individuals. There was no discernible pattern in the order in which long and short hairs were secreted on the periostracal surfaces of either valve. Byssal hair microstructure was generally consistent with the distal region of byssal threads, having a tough but thin outer cortex surrounding a ‘spongy’ honeycomb matrix.

Developmental validation of the HIrisPlex system: DNA-based eye and hair colour prediction for forensic and anthropological usage

Forensic DNA Phenotyping or 'DNA intelligence' tools are expected to aid police investigations and find unknown individuals by providing information on externally visible characteristics of unknown suspects, perpetrators and missing persons from biological samples. This is especially useful in cases where conventional DNA profiling or other means remain non-informative. Recently, we introduced the HIrisPlex system, capable of predicting both eye and hair colour from DNA. In the present developmental validation study, we demonstrate that the HIrisPlex assay performs in full agreement with the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines providing an essential prerequisite for future HIrisPlex applications to forensic casework. The HIrisPlex assay produces complete profiles down to only 63 pg of DNA. Species testing revealed human specificity for a complete HIrisPlex profile, while only non-human primates showed the closest full profile at 20 out of the 24 DNA markers, in all animals tested. Rigorous testing of simulated forensic casework samples such as blood, semen, saliva stains, hairs with roots as well as extremely low quantity touch (trace) DNA samples, produced complete profiles in 88% of cases. Concordance testing performed between five independent forensic laboratories displayed consistent reproducible results on varying types of DNA samples. Due to its design, the assay caters for degraded samples, underlined here by results from artificially degraded DNA and from simulated casework samples of degraded DNA. This aspect was also demonstrated previously on DNA samples from human remains up to several hundreds of years old. With this paper, we also introduce enhanced eye and hair colour prediction models based on enlarged underlying databases of HIrisPlex genotypes and eye/hair colour phenotypes (eye colour: N = 9188 and hair colour: N = 1601). Furthermore, we present an online web-based system for individual eye and hair colour prediction from full and partial HIrisPlex DNA profiles. By demonstrating that the HIrisPlex assay is fully compatible with the SWGDAM guidelines, we provide the first forensically validated DNA test system for parallel eye and hair colour prediction now available to forensic laboratories for immediate casework application, including missing person cases. Given the robustness and sensitivity described here and in previous work, the HIrisPlex system is also suitable for analysing old and ancient DNA in anthropological and evolutionary studies.

Tonotopic Morphometry of the Lamina Reticularis of the Guinea Pig Cochlea with Associated Microstructures and Related Mechanical Implications

Morphometry of the lamina reticularis of the guinea pig cochlea was performed using scanning electron microscopy. Seventy-four geometrical parameters of the lamina reticularis, the bundles of stereocilia, and individual stereocilia, in all rows of hair cells and within the individual hair cells, were measured at ten equally spaced locations along the longitudinal direction of the cochlea. Variations of the parameters versus the longitudinal coordinate were statistically analyzed and fitted with polynomials (constant, linear, or quadratic). Our data show that a unique set of geometrical parameters of inner and outer hair cells is typical for every frequency-dependent position at the lamina reticularis. Morphology of the outer hair cell structures varies more than respective parameters of the inner hair cells. Mechanical modeling using the obtained geometrical parameters provides a novel glance at the mechanical characteristics with respect to the cochlear tonotopy.

Enhanced signal-to-noise ratios in frog hearing can be achieved through amplitude death

In the ear, hair cells transform mechanical stimuli into neuronal signals with great sensitivity, relying on certain active processes. Individual hair cell bundles of non-mammals such as frogs and turtles are known to show spontaneous oscillation. However, hair bundles in vivo must be quiet in the absence of stimuli, otherwise the signal is drowned in intrinsic noise. Thus, a certain mechanism is required in order to suppress intrinsic noise. Here, through a model study of elastically coupled hair bundles of bullfrog sacculi, we show that a low stimulus threshold and a high signal-to-noise ratio (SNR) can be achieved through the amplitude death phenomenon (the cessation of spontaneous oscillations by coupling). This phenomenon occurs only when the coupled hair bundles have inhomogeneous distribution, which is likely to be the case in biological systems. We show that the SNR has non-monotonic dependence on the mass of the overlying membrane, and find out that the SNR has maximum value in the region of amplitude death. The low threshold of stimulus through amplitude death may account for the experimentally observed high sensitivity of frog sacculi in detecting vibration. The hair bundles' amplitude death mechanism provides a smart engineering design for low-noise amplification.

Spectroscopic Studies of Human Hair, Nail, and Saliva Samples Using a Cantilever-Based Photoacoustic Detection

In infrared spectroscopy human hair has normally been studied using attenuated total reflectance or diffuse reflectance infrared Fourier transform spectroscopy, for which the sample preparation methods can lead to problems of reproducibility. Definite information could be obtained by studying intact individual hair fibers, but the small diameter of hair fibers and the lack of sensitivity make such measurement difficult. A highly detailed infrared spectrum of human hair has been measured using a cantilever-based photoacoustic detection. The spectrum can be obtained even if a piece of hair as small as 1 cm is used as a sample. Photoacoustic spectroscopy (PAS) is a well-established technique in many areas, but very little has been published in the research of proteins. Two simple applications of PAS for human hair, as well as measurements with different types of proteins, are presented in this paper.

Investigating the origins of nanostructural variations in differential ethnic hair types using X‐ray scattering techniques

Human hair is a major determinant of visual ethnic differentiation. Although hair types are celebrated as part of our ethnic diversity, the approach to hair care has made the assumption that hair types are structurally and chemically similar. Although this is clearly not the case at the macroscopic level, the intervention of many hair treatments is at the nanoscopic and molecular levels. The purpose of the work presented here is to identify the main nanoscopic and molecular hierarchical differences across five different ethnic hair types from hair fibres taken exclusively from the scalp. These are Afro (subdivided into elastic 'rubber' and softer non-elastic 'soft'), Chinese, European and Mullato (mixed race). Small angle X-Ray scattering (SAXS) is a technique capable of resolving nanostructural variations in complex materials. Individual hair fibres from different ethnic hair types were used to investigate structural features found in common and also specific to each type. Simultaneous wide angle X-Ray scattering (WAXS) was used to analyse the submolecular level structure of the fibrous keratin present. The data sets from both techniques were analysed with principal component analysis (PCA) to identify underlying variables. Principal component analysis of both SAXS and WAXS data was shown to discriminate the scattering signal between different hair types. The X-ray scattering results show a common underlying keratin intermediate filament (KIF) structure. However, distinct differences were observed in the preferential orientation and intensity signal from the lipid component of the hair. In addition, differences were observed in the intensity distribution of the very low-angle sample-dependent diffuse scatter surrounding the 'beamstop.' The results indicate that the fibrous keratin scaffold remains consistent between ethnic hair types. The hierarchies made by these may be modulated by variation in the content of keratin-associated proteins (KAPs) and lipids that alter the interfacial structures and lead to macroscopic differences in hair morphology.

High resolution synchrotron imaging of wheat root hairs growing in soil and image based modelling of phosphate uptake

· Root hairs are known to be highly important for uptake of sparingly soluble nutrients, particularly in nutrient deficient soils. Development of increasingly sophisticated mathematical models has allowed uptake characteristics to be quantified. However, modelling has been constrained by a lack of methods for imaging live root hairs growing in real soils. · We developed a plant growth protocol and used Synchrotron Radiation X-ray Tomographic Microscopy (SRXTM) to uncover the three-dimensional (3D) interactions of root hairs in real soil. We developed a model of phosphate uptake by root hairs based directly on the geometry of hairs and associated soil pores as revealed by imaging. · Previous modelling studies found that root hairs dominate phosphate uptake. By contrast, our study suggests that hairs and roots contribute equally. We show that uptake by hairs is more localized than by roots and strongly dependent on root hair and aggregate orientation. · The ability to image hair-soil interactions enables a step change in modelling approaches, allowing a more realistic treatment of processes at the scale of individual root hairs in soil pores.

Abstract 3350: Plucked hair as a biomarker platform for monitoring transcriptional consequences of clinical exposure to antagonism of the HDM2/P53 interaction in tumors.

Abstract The ability to assess and monitor target engagement is crucial for informing early drug development decisions. High vascularisation of the hair follicle, frequent epithelial origin of tumors, and high degree of congruence of expression in hair of pathways dysregulated in cancers, makes the cellular bulb on plucked human scalp hair an excellent surrogate tissue for non-invasive monitoring of PD effects in clinical trials. Disruption of the p53-HDM2 interaction with small molecules has demonstrated single agent anti-tumor activity in preclinical models and represents an attractive treatment strategy in oncology. Development of a peripheral tissue based gene expression signature of inhibition of the p53-HDM2 interaction could facilitate the early development of these compounds. To develop a peripheral PD biomarker of antagonism of this interaction, we used two selective p53-HDM2 antagonists, Nutlin-3 and Sanofi's SAR405838 and applied our plucked hair biomarker platform to develop a gene expression signature indicative of compound exposure. SAR405838 displays potent activity in vitro and in vivo against p53 WT cell lines / xenograft models, but not in the p53 mutant context. Three hairs from each of four healthy donors were exposed to either SAR405838 or Nutlin-3 over a range of compound concentrations for 6hr or 24hr in our proprietary ex vivo cultures. We extracted RNA from the cellular bulb of individual hairs and assessed the transcriptome by microarray analysis. Biological enrichment analysis of genes differentially expressed revealed strong correlation to activated P53 signaling pathways. Further analysis revealed a core set of congruent genes as candidate PD biomarkers of p53-HDM2 antagonism, one of which was MIC-1, a secreted plasma protein that demonstrates a strong PK/PD relationship in patients treated with p53-MDM2 antagonists in Phase 1 trials. In ex vivo plucked hair, we have demonstrated biologically relevant differential expression of a panel of transcriptional markers exhibiting common response to Nutlin-3 and SAR405838. These reflect compound mechanism of action, and can provide further evidence of target engagement in addition to plasma MIC-1 levels. While the temporal and kinetic relationship between gene expression changes, toxicity, and clinical efficacy remains to be determined, the genes identified in this study may be used to provide further MOA information in clinical settings to monitor PD responses in plucked scalp hair obtained from patients exposed to SAR405838. Citation Format: Gino Miele, Elliot Harrison, Tim Mefo, Jo Read, Lydia Meyer Turkson, Alan Murdoch, Michael Teufel, Laurent Debussche, Donald Bergstrom, James Watters. Plucked hair as a biomarker platform for monitoring transcriptional consequences of clinical exposure to antagonism of the HDM2/P53 interaction in tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3350. doi:10.1158/1538-7445.AM2013-3350

Power Amplification and Selectivity in the Cochlear Amplifier

Abstract This paper presents a new model that describes the physical phenomena occurring in an individual Outer Hair Cell (OHC) in the human hearing organ (Cochlea). The new model employs the concept of parametric amplification and piezoelectricity. As a consequence, the proposed model may explain in a natural way many as yet unresolved problems about the mechanisms of: 1) power amplification, 2) non- linearity, 3) fine tuning, or 4) high sensitivity that take place in the human hearing organ. Mathematical analysis of the model is performed. The equivalent electrical circuits of an individual OHC are established. The high selectivity of the OHC parametric amplifier is analyzed by solving the resulting Mathieu and Ince differential equations. An analytical formula for the power gain in the OHC’s parametric amplifier has been developed. The proposed model has direct physical interpretation and all its elements have their physical counterparts in the actual structure of the cochlea. The numerical values of the individual elements of the electrical equivalent circuits are consistent with the experimental physiological data. It is anticipated that the proposed new model may contribute in future improvements of human cochlear implants as well as in development of new digital audio standards.

Tuning and Timing in Mammalian Type I Hair Cells and Calyceal Synapses

Afferent nerve fibers in the central zones of vestibular epithelia form calyceal endings around type I hair cells and have phasic response properties that emphasize fast head motions. We investigated how stages from hair-cell transduction to calyceal spiking contribute tuning and timing to central (striolar)-zone afferents of the rat saccular epithelium. In an excised preparation, we deflected individual hair bundles with rigid probes driven with steps and sinusoids (0.5-500 Hz) and recorded whole-cell responses from hair cells and calyces at room temperature and body temperature. In immature hair cells and calyces (postnatal days (P)1-P4), tuning sharpened at each stage. Transducer adaptation and membrane-charging time produced bandpass filtering of the receptor potential with best frequencies of 10-30 Hz and phase leads below 10 Hz. For small stimuli, electrical resonances sharply tuned the hair-cell membrane in the frequency range of 5-40 Hz. The synaptic delay of quantal transmission added a phase lag at frequencies above 10 Hz. The influence of spike thresholds at the calyceal spike initiation stage sharpened tuning and advanced response phase. Two additional mechanisms strongly advanced response phase above 10 Hz when present: (1) maturing (P7-P9) type I hair cells acquired low-voltage-activated channels that shortened the rise time of the receptor potential and (2) some calyces had nonquantal transmission with little synaptic delay. By reducing response time, the identified inner-ear mechanisms (transducer adaptation, low-voltage-activated channels, nonquantal transmission, and spike triggering) may compensate for transmission delays in vestibular reflex pathways and help stabilize posture and gaze during rapid head motions.

Androgenetic alopecia and risk of prostate cancer: A systematic review and meta-analysis

Androgenetic alopecia (AGA) is a genetically determined skin condition strongly age dependent and androgens are assumed to play an important role in its development. A link between AGA and prostate cancer has been hypothesized because of their similar risk factors. We sought to systematically review the evidence available on the association between AGA and risk of prostate cancer. We searched the electronic databases MEDLINE and Cochrane for studies examining the association between AGA and risk of prostate cancer. We estimated pooled odds ratios (OR) and 95% confidence intervals. We also analyzed the OR for individual hair loss patterns, as defined by the Hamilton scale. A total of 7 case-control studies including 8994 patients-4078 cases and 4916 controls-were reviewed. One cohort study was identified but did not meet our inclusion criteria. There was statistically significant association between vertex baldness and prostate cancer (OR 1.25; 95% confidence interval 1.09-1.44; Z = 3.13; P = .002). No statistically significant association between AGA (any pattern) and prostate cancer was identified (OR 1.03; 95% confidence interval 0.93-1.13; Z = 0.55; P = .58). Only case-control studies, which may be subject to bias, met the inclusion criteria for this meta-analysis. Vertex pattern AGA was associated with a significant increased risk of prostate cancer. Any pattern AGA did not show a significant increase in the risk of prostate cancer.

Premature graying of hair

Premature graying is an important cause of low self-esteem, often interfering with socio-cultural adjustment. The onset and progression of graying or canities correlate very closely with chronological aging, and occur in varying degrees in all individuals eventually, regardless of gender or race. Premature canities may occur alone as an autosomal dominant condition or in association with various autoimmune or premature aging syndromes. It needs to be differentiated from various genetic hypomelanotic hair disorders. Reduction in melanogenically active melanocytes in the hair bulb of gray anagen hair follicles with resultant pigment loss is central to the pathogenesis of graying. Defective melanosomal transfers to cortical keratinocytes and melanin incontinence due to melanocyte degeneration are also believed to contribute to this. The white color of canities is an optical effect; the reflection of incident light masks the intrinsic pale yellow color of hair keratin. Full range of color from normal to white can be seen both along individual hair and from hair to hair, and admixture of pigmented and white hair is believed to give the appearance of gray. Graying of hair is usually progressive and permanent, but there are occasional reports of spontaneous repigmentation of gray hair. Studies evaluating the association of canities with osteopenia and cardiovascular disease have revealed mixed results. Despite the extensive molecular research being carried out to understand the pathogenesis of canities, there is paucity of effective evidence-based treatment options. Reports of repigmentation of previously white hair following certain inflammatory processes and use of drugs have suggested the possibility of cytokine-induced recruitment of outer sheath melanocytes to the hair bulb and rekindled the hope for finding an effective drug for treatment of premature canities. In the end, camouflage techniques using hair colorants are outlined.

Higher-Order Mode-Locking and Phase Slips in Hair Cell of the Inner Ear

Auditory system is known for its exquisite sensitivity, displaying sub-nanometer detection thresholds. Mechanical deflections evoked by external sound and ground vibrations are converted by the inner ear hair cells into electrical signals. In some species, hair cell bundles exhibit spontaneous oscillations under in vitro conditions. In Bullfrog sacculus, the oscillation profile is consistent with relaxation-type oscillation, in which a rapid motion of a bundle is followed by a slow drift along the same direction. A large number of hair bundles also show more complex temporal profiles, with quiescent intervals interspersed with bursts of oscillation. We study the dynamics of phase-locking of individual hair bundles to low-amplitude mechanical stimulations, where the amplitude of the oscillations remains unaffected by the stimulus. Under low-frequency stimulation, the signal entrains the bundle motility via higher-order mode-locking. The applied signal modulated both the quiescent intervals and the oscillatory bursts, across a broad range of frequencies. We compare these experimental findings with results from numerical simulations.

Disappearance of 6-acetylmorphine, morphine and codeine from human scalp hair after discontinuation of opiate abuse

Opiates continue to be used at high rates in East and Southeast Asia. Hair analysis for drugs of abuse has been developed into a powerful and widely used tool in forensic and clinical toxicology. Specifically, testing the proximal segment of scalp hair to confirm morphine (MOR) positive urine samples could solve the poppy seed problem. Human scalp hair grows approximately 1cm per month and can therefore reflect a retrospective timeline of drug exposure. This study is the first to investigate the disappearance of 6-acetylmorphine (6-AM), MOR and codeine (COD) from human scalp hair after the discontinuation of drug use. Thirty-two healthy women (ages 21–51 years) with a known history of heroin abuse, who went to a rehabilitation centre and ceased consuming heroin (for 4–5 months), were recruited into the study. A pharmacokinetic analysis in seven individual hair segments was performed using a first-order kinetic. Assuming a rate of hair growth of 1cm/month, the mean hair elimination half-lives of 6-AM, MOR and COD were 0.88 months (95% CI, 0.74–1.03), 0.73 months (95% CI, 0.64–0.81), and 0.61 months (95% CI, 0.54–0.69), respectively. Our results suggest that to evaluate the discontinuation of opiate abuse after a 6-month period of abstinence, the results from a 3-cm proximal hair segment should be free of 6-AM at the proposed 0.2ng/mg cutoff level. This finding should become the basis for the interpretation of results from segmental hair analyses in the evaluation of drug abstinence.

Hair cortisol levels determined at different body sites in the New Zealand White rabbit

This study was designed to determine hair cortisol levels in the New Zealand White (NZW) rabbit and to examine possible differences in the cortisol levels of hair samples collected from different body regions in stable environmental conditions. The experiment was performed on eight 18 month-old female NZW rabbits. All animals were shaved to collect hair samples from 26 different body regions. Hair cortisol levels were determined by the RIA method. The mean hair cortisol concentration for the 26 samples in the 8 animals was 2.12±0.05 pg/mg (mean±standard error). This study reveals individual hair cortisol distributions in the 8 animals (P<0.001) and no statistical differences (P>0.05) in hair cortisol levels among the different body sites in each of the animals.

Frequency-selective exocytosis by ribbon synapses of hair cells in the bullfrog's amphibian papilla.

The activity of auditory afferent fibers depends strongly on the frequency of stimulation. Although the bullfrog's amphibian papilla lacks the flexible basilar membrane that effects tuning in mammals, its afferents display comparable frequency selectivity. Seeking additional mechanisms of tuning in this organ, we monitored the synaptic output of hair cells by measuring changes in their membrane capacitance during sinusoidal electrical stimulation at various frequencies. Using perforated-patch recordings, we found that individual hair cells displayed frequency selectivity in synaptic exocytosis within the frequency range sensed by the amphibian papilla. Moreover, each cell's tuning varied in accordance with its tonotopic position. Using confocal imaging, we observed a tonotopic gradient in the concentration of proteinaceous Ca(2+) buffers. A model for synaptic release suggests that this gradient maintains the sharpness of tuning. We conclude that hair cells of the amphibian papilla use synaptic tuning as an additional mechanism for sharpening their frequency selectivity.

Towards a high-resolution flow camera using artificial hair sensor arrays for flow pattern observations

Flow-sensor arrays uncover the potential to measure spatio-temporal flow patterns rather than flow measurements at just a single point. We present in this paper the developments in design, fabrication and interfacing of biomimetic flow-sensor arrays, inspired by flow-sensitive organs (cerci) of crickets. For the purpose of high-resolution flow field visualization by our artificial hair flow-sensor arrays, various array-interfacing schemes are discussed and compared. Frequency division multiplexing (FDM) is shown to be an attractive method for efficient interrogation of capacitive array sensors. Using silicon-on-insulator technology with deep trench isolation structures, hair-based flow-sensors with differential capacitive read-out, arranged in single-chip arrays, have been successfully fabricated. FDM is implemented and used to interrogate individual hair sensors providing simultaneous real-time flow measurements from multiple hairs. This powerful approach is demonstrated by reconstruction of the field of a harmonic dipole field at the position of the hairs and by localizing this dipole source relative to the array elements.

Influence of urban edges on stress in an arboreal mammal: a case study of squirrel gliders in southeast Queensland, Australia

There is growing recognition that ecological research must expand its focus beyond inference based on pattern-process relationships to the direct measurement of ecological and physiological processes. Physiological assessment is important because vertebrates cope with unpredictable and noxious stimuli by initiating a stress response. However, an over-activation of the acute stress response by numerous novel and potentially stressful anthropogenic pressures, including those associated with urban edges, has the potential to generate chronic stress and a greater susceptibility to disease, reduce fecundity and survivorship. An individual’s physiological response to edge habitats with varying degrees of contrast to the adjacent disturbed urban matrix (e.g. major vs. minor roads), may provide insight into their survival likelihood in fragmented urban landscapes. Although demographic changes in wildlife resulting from urbanization have been documented, only recently have physiological consequences been examined. We addressed this problem using a case study of the squirrel glider (Petaurus norfolcensis) in the fragmented urban landscape of southeast Queensland, Australia. Hair samples were used to enable a comparison of hair cortisol levels in individual squirrel gliders, providing an indication of potential stress. We applied a linear mixed-effect modeling approach clustered by patch to quantify the influence of site-level habitat factors and relative abundance comparative to edge contrast on hair cortisol levels. We found that edge type had a strong positive effect on hair cortisol levels; but this depended on the availability of abundant nest hollows at a site. We conclude that individual hair cortisol concentration, providing an index of stress, was lowest in interior habitats and highest in edge habitats adjacent to major roads. Furthermore, gliders occupying low edge contrast habitats adjacent to residential areas and minor roads, and containing abundant tree nest hollows, had low-moderate hair cortisol levels. This highlights the potential importance of these habitats for the conservation of arboreal mammals such as the squirrel glider in urban landscapes.

Kinocilia Mediate Mechanosensitivity in Developing Zebrafish Hair Cells

Mechanosensitive cilia are vital to signaling and development across many species. In sensory hair cells, sound and movement are transduced by apical hair bundles. Each bundle is comprised of a single primary cilium (kinocilium) flanked by multiple rows of actin-filled projections (stereocilia). Extracellular tip links that interconnect stereocilia are thought to gate mechanosensitive channels. In contrast to stereocilia, kinocilia are not critical for hair-cell mechanotransduction. However, by sequentially imaging the structure of hair bundles and mechanosensitivity of individual lateral-line hair cells invivo, we uncovered a central role for kinocilia in mechanosensation during development. Our data demonstrate that nascent hair cells require kinocilia and kinocilial links for mechanosensitivity. Although nascent hair bundles have correct planar polarity, the polarity of their responses to mechanical stimuli is initially reversed. Later in development, a switch to correctly polarized mechanosensitivity coincides with the formation of tip links and the onset of tip-link-dependent mechanotransduction.

Tonotopic Relationships Reveal the Charge Density Varies along the Lateral Wall of Outer Hair Cells

Outer hair cells amplify and improve the frequency selectivity of sound within the mammalian cochlea through a sound-evoked receptor potential that induces an electromechanical response in their lateral wall membrane. We experimentally show that the membrane area and linear membrane capacitance of outer hair cells increases exponentially with the electrically evoked voltage-dependent charge movement (QT) and peak membrane capacitance (Cpeak). We determine the size of the different functional regions (e.g., lateral wall, synaptic basal pole) of the polarized cells from the tonotopic relationships. We then establish that QT and Cpeak increase with the logarithm of the lateral wall area (ALW) and determine from the functions that the charge (σLW, pC/μm2) and peak (ρLW, pF/μm2) densities vary inversely with ALW (σLW = 1.3/ALW and ρLW = 9/ALW). This shows contrary to conventional wisdom that σLW and ρLW are not constant along the length of an individual outer hair cell.