Three-row stereocilia model predicts mammalian hair bundle behavior

Abstract

Mammalian outer hair cells (OHCs) enhance sound amplification and frequency tuning through stereociliary hair bundles (HBs), which convert mechanical motion into electrical signals via mechano-electric transducer (MET) channels. Experiments show that the HB displacement creeps, and the MET current evinces dual timescales of adaptation in response to mechanical stimulus. Understanding these mechanisms is crucial for elucidating normal auditory function and disorders, yet their origins remain unclear. To address this, we developed a mathematical model of the OHC HB that incorporates three rows of stereocilia with distinct nonlinear adaptive gating mechanisms, nonlinear kinematics, and viscoelastic mechanics. Our model accurately replicates experimental responses to fluid-jet stimulation, predicting simultaneous mechanical creep and slow adaptation of the MET current. Using stiff probe stimulation, the same model reveals even faster adaptation, aligning with experimental observations and emphasizing the stimulus-dependence of the response. The model provides new insights into the functional importance of the three-row stereocilia configuration, offering a mechanistic explanation for its ubiquity in mammalian HBs and its role in facilitating the complex timescales of adaptation.