The auditory portion of the mammalian inner ear, the cochlea, transduces sound waves into electrical energy. There are progressive changes in the basilar membrane, the dominant vibratory element of the cochlea, that create a tonotopic organization. Thus, one end of the cochlea resonates at high frequencies and the other at low frequencies. At normal speech intensities, the magnitude of basilar membrane vibrations ranges from 0.1 -1 nm. Loud sounds, aging, and ototoxic medications cause hearing loss by damaging the sensory hair cells that sit on top of the basilar membrane. These insults predominantly cause hair cell death in the high frequency region of the cochlea while the hair cells in the low frequency region remain essentially intact. We propose to use laser irradiation to retune the resonant frequency map of the basilar membrane by modulating the nano-scale organization of its constituent collagen molecules. The clinical significance of this technique is the potential for development of a novel treatment for patients with hearing loss by making the low frequency region of the cochlea that contains functional hair cells to be more sensitive to high frequency sounds. We have already demonstrated using histological techniques that laser irradiation can induce molecular changes in the structure of collagen within the basilar membrane. In other tissues, similar laserinduced changes in collagen change the tissue stiffness. We hypothesize that laser-induced nanoscale structural changes within the basilar membrane will similarly change the stiffness of the basilar membrane and subsequently alter the resonant frequency map. We will test this hypothesis by using a laser Doppler vibrometer to measure basilar membrane resonance in the mouse cochlea before and after laser irradiation. Additionally, auditory brainstem evoked responses, an in vivo measure of hearing, will be measured before and after irradiation. Finally, light and electron microscopy will be used to assess for histological changes in the irradiated cochlea. This proposal represents a collaborative effort between John S. Oghalai, MD (a clinician-scientist ear specialist at Baylor College of Medicine) and Bahman Anvari, PhD (a biomedical engineer with expertise in optics and lasers at Rice University). We believe this proposal meets the goals of the Alliance for NanoHealth because it involves the use of novel bioengineering technology to modulate the nano-mechanical properties of collagen within a biologic organ that functions to detect nano-scale vibrations.