The research objective of this award is to explore synchronization of motion among hair cells of the inner ear, and its role in the overall sensitivity of mechanical detection. The PI will create a hybrid system, in which a biological preparation containing live and functional cells is interfaced with artificial polymer membranes. This will enable direct measurements of the onset and dynamics of synchronization between oscillatory cells. Polymer membranes of different material properties will be used to allow variation in the strength of inter-cell connections, and their sizes will be varied so as to couple different numbers of elements. Electronic circuits will also be introduced that mimic the role of neural control of hair cells. Voltage signals will be applied across the sensory epithelium in conjunction with the mechanical sensitivity measurements, and a feedback circuit will maximize the responsiveness of the preparation. The hybrid preparation will provide a system in which coupling and adaptive behavior can be independently varied, and hence the role of these two important elements can be quantitatively assessed.
Nanoscale sensitivity of detection by the auditory system has still not been fully explained, and these experiments are designed to identify the missing components in our understanding of its underlying mechanisms. The project constitutes the first step towards the construction of a bio-mimetic device that can replicate the behavior of the cochlea, with the long-term goal of creating an implantable artificial mechanical sensor. The educational efforts of the PI aim to train graduate and undergraduate students in techniques at the interface of physics, engineering, and biology, via new courses introduced into the curriculum, undergraduate research programs, and an inter-departmental discussion forum.
Hair cells of the inner ear constitute the mechanical sensors performing the detection of sound. The remarkable sensitivity, dynamic range, and frequency selectivity of the auditory system have been actively studied for decades, yet still remain incompletely explained. One of the crucial elements underlying this extreme sensitivity of detection is an active amplification process, which has been demonstrated in a number of in vivo and in vitro experiments. One of the signatures of the active process, observed in several species, is an innate oscillation of the hair cell bundle. Comparisons to theoretical predictions have proven that this spontaneous motility requires an energy-consuming process. This phenomenon is therefore one of the manifestations of an internal amplifier and has been used to explore the nonlinear dynamics of hair bundle response. In this project, we hypothesized that that coupling between cells is an important element in achieving the extreme sensitivity of detection, and we explored this effect in a hybrid bio-mechanical system in which this term can be carefully controlled. We used the epithelium of the bullfrog sacculus, with the natural overlying membrane removed, and interfaced it with artificial components of varying dimensions and elastic properties. The number of hair cells coupled and the strength of the coupling terms were varied. We found that robust synchronization occurs between spontaneously oscillating hair cell bundles, coupled by an overlying microsphere. This was true even when the individual oscillators showed very different frequencies. The data showed that the collective spontaneous motility of the hair bundles produced enough force to drive the much larger overlying bead. This indicates that such active innate motility, if entrained among a number of hair cells, could underlie phenomena such as spontaneous otoacoustic emissions. We further observed that oscillations in the coupled system were more regular, showing reduced variation in the instantaneous frequency, compared to that typically observed in individual hair cells. Hence, the coupled system demonstrated sharpening of the frequency distribution. This is consistent with theoretical predictions, indicating that coupled systems show an enhanced performance compared to individual oscillators. The use of a hybrid preparation where semi-intact, biologically functional, epithelia are interfaced with artificial elements will provide us with a unique system in which we can independently control and explicitly assess the role of inter-cell coupling. The complexity of the biological system merits the approach of reverse-engineering, where one element at a time is replaced with an artificial component. These results constitute a first step in the longer-term study, that could lead to an improved mechanical sensor to replace a damaged cochlea. The nature of this research is inherently interdisciplinary, and the educational efforts of the PI were aimed at training a generation of scientists that will excel at this interface. The PI has introduced a laboratory class on biophysics, participated in a number of undergraduate research programs, and has launched an inter-departmental discussion forum, all with the goal of building a diverse and interactive environment for young researchers in this field.
