Hair cells, the sensory receptors of the internal ear, subserve different functions in various receptor organs: they detect oscillatory stimuli in the auditory system, but transduce constant and step stimuli in the vestibular and lateral-line systems. We show that a hair cell's function can be controlled experimentally by adjusting its mechanical load. By making bundles from a single organ operate as any of four distinct types of signal detector, we demonstrate that altering only a few key parameters can fundamentally change a sensory cell's role. The motions of a single hair bundle can resemble those of a bundle from the amphibian vestibular system, the reptilian auditory system, or the mammalian auditory system, demonstrating an essential similarity of bundles across species and receptor organs.auditory system | dynamical system | hair cell | Hopf bifurcation | vestibular system T he hair bundles of vertebrates are mechanosensory organelles responsible for detecting sounds in the auditory system, linear and angular accelerations in the vestibular system, and water movements and pressure gradients in the lateral-line system of fishes and amphibians (1, 2). In each instance an appropriate stimulus deflects the bundles, depolarizing the hair cells from which they emerge (3). Hair bundles are not simply passive detectors, however, for they actively amplify their responses to mechanical stimulation (4, 5). Hair-bundle motility contributes to an active process that endows the auditory system with the ability to detect stimuli with energies near that of thermal fluctuations (6), to distinguish tones that differ by less than 0.2% in frequency (7), and to accommodate inputs varying over a millionfold range in amplitude (4,(8)(9)(10)(11).Auditory, vestibular, and lateral-line organs respond to distinct patterns of mechanical input. The mechanical properties and environments of hair bundles differ correspondingly between different organisms, among receptor organs, and with the tonotopic position along individual auditory organs (12-15). A mathematical model predicts that the response of a hair bundle is regulated both by its intrinsic mechanical characteristics and by its mechanical load (16). Motivated by this proposition, we investigated how the load stiffness and constant force imposed on a bundle control its dynamics and response to external perturbations. ResultsMapping the Hair Bundle's Experimental State Diagram. The hair bundle's state diagram characterizes its behavior for different combinations of two control parameters: load stiffness, or force per unit displacement, and constant force. These control parameters describe the mechanical load imposed on a hair bundle within a sensory organ. A theoretical model of hair-bundle dynamics predicts the qualitative structure of the state diagram ( Fig. 1 A-C). To test this prediction experimentally, we varied the mechanical load imposed on an individual hair bundle and monitored its displacement. The load was delivered to an individual hair bundle by attaching the tip o...

Dysfunctions of hearing and balance are often irreversible in mammals owing to the inability of cells in the inner ear to proliferate and replace lost sensory receptors. To determine the molecular basis of this deficiency we have investigated the dynamics of growth and cellular proliferation in a murine vestibular organ, the utricle. Based on this analysis, we have created a theoretical model that captures the key features of the organ’s morphogenesis. Our experimental data and model demonstrate that an elastic force opposes growth of the utricular sensory epithelium during development, confines cellular proliferation to the organ’s periphery, and eventually arrests its growth. We find that an increase in cellular density and the subsequent degradation of the transcriptional cofactor Yap underlie this process. A reduction in mechanical constraints results in accumulation and nuclear translocation of Yap, which triggers proliferation and restores the utricle’s growth; interfering with Yap’s activity reverses this effect.DOI: http://dx.doi.org/10.7554/eLife.25681.001

As the health care delivery landscape changes, medical schools must develop creative strategies for preparing future physicians to provide quality care in this new environment. Despite the growing prominence of the patient-centered medical home (PCMH) as an effective model for health care delivery, few medical schools have integrated formal education on the PCMH into their curricula. Incorporating the PCMH model into medical school curricula is important to ensure that students have a comprehensive understanding of the different models of health care delivery and can operate effectively as physicians. The authors provide a detailed description of the process by which the Weill Cornell Community Clinic (WCCC), a student-run free clinic, has integrated PCMH principles into a service-learning initiative. The authors assessed patient demographics, diagnoses, and satisfaction along with student satisfaction. During the year after a PCMH model was adopted, 112 students and 19 licensed physicians volunteered their time. A review of the 174 patients seen from July 2011 to June 2012 found that the most common medical reasons for visits included management of hypertension, hyperlipidemia, diabetes, gastrointestinal conditions, arthritis, anxiety, and depression. During the year after the adoption of the PCMH model, 87% were very or extremely satisfied with their care, and 96% of the patients would recommend the WCCC to others. Students who participate in the WCCC gain hands-on experience in coordinating care, providing continuity of care, addressing issues of accessibility, and developing quality and safety metrics. The WCCC experience provides an integrative model that links service-learning with education on health care delivery in a primary care setting. The authors propose that adoption of this approach by other student-run clinics provides a substantial opportunity to improve medical education nationwide and better prepare future physicians to practice within this new model of health care delivery.