  Mechanoelectrical transduction in the inner ear is a biophysical process
underlying the senses of hearing and balance. The key players involved in this
process are mechanosensitive ion channels. They are located in the stereocilia
of hair cells and opened by the tension in specialized molecular springs, the
tip links, connecting adjacent stereocilia. When channels open, the tip links
relax, reducing the hair-bundle stiffness. This gating compliance makes hair
cells especially sensitive to small stimuli. The classical explanation for the
gating compliance is that the conformational rearrangement of a single channel
directly shortens the tip link. However, to reconcile theoretical models based
on this mechanism with experimental data, an unrealistically large structural
change of the channel is required. Experimental evidence indicates that each
tip link is a dimeric molecule, associated on average with two channels at its
lower end. It also indicates that the lipid bilayer modulates channel gating,
although it is not clear how. Here, we design and analyze a model of
mechanotransduction where each tip link attaches to two channels, mobile within
the membrane. Their states and positions are coupled by membrane-mediated
elastic forces arising from the interaction between the channels' hydrophobic
cores and that of the lipid bilayer. This coupling induces cooperative opening
and closing of the channels. The model reproduces the main properties of
hair-cell mechanotransduction using only realistic parameters constrained by
experimental evidence. This work provides an insight into the fundamental role
that membrane-mediated ion-channel cooperativity can play in sensory
physiology.
