Below ~200 Hz optimum stereocilium lengths predicted by flexoelectricity deviate from the lengths observed in nature (, −1/8 slope). Hence, if hair-bundle flexoelectricity were important at low frequencies, the motor would be inefficient. This suggests that other motor mechanisms associated with the MET molecular apparatus, such as unconventional myosin motors showing climbing and sliding rate limitations of 100 Hz and 44 Hz 
, respectively, or somatic motility
might have advantages at low frequencies. It is interesting that human hearing spans this range, as does hearing in many mammals including dogs, cats, guinea pigs and chinchillas. This opens the possibility that mammals may take advantage of one motor mechanism dominating at low frequencies and a different motor mechanism dominating at high frequencies. Present results show that stereocilia membrane flexoelectricity would be particularly tuned and efficient at high frequencies.
Support for the flexoelectric hypothesis also comes from genetic models of inherited hearing disorders. Flexoelectricity predicts that genetic models disrupting transverse connective links between adjacent stereocilia and/or disrupting the staircase ultrastructure of the bundle would result in impaired function of the cochlear amplifier. This is indeed the case. In adult myosin-XVa-deficient shaker 2 mice, the staircase architecture of hair bundles is lost and severe hearing loss occurs. Interestingly, these mice have nearly normal MET currents 
. The present model predicts zero power output for these hair bundles because axial flexoelectric motion would not drive transverse deflection (see Eq. 10) and the power output would be zero. Similar results are found in stereocilin-deficient mice that lack horizontal top connectors, lateral links that connect adjacent stereocilia together 
. The present analysis predicts hearing loss in both of these animal models due to disruption of the axial-transverse coupling normally exploited by the flexoelectric hair-bundle motor. There is evidence 
suggesting that the tip-link insertion may not be near the top of the stereocilia, If this translates to the location of the MET current entering stereocilia, the primary effect would be to shorten the electrical path to the soma and thereby reduce the axial conductance. Such an arrangement would shift the most efficient frequency up slightly – by approximately
is the distance from the base to the MET channel and
is the total length of the cilia.
Mechanical amplification of sound signals in the inner ear is controlled by the brain, in most species, through extensive efferent synaptic contacts on hair cells. In mammals, activation of the efferent system decreases mechanical amplification within the cochlea primarily through efferent action on outer hair cells 
. A similar amplification control strategy is present in birds where efferent neurons contact short hair cells while afferents exclusively contact long sensory hair cells. The short hair cells in birds do not exhibit prestin dependent electromotility 
, but do have motile hair bundles thus implicating efferent innervation is controlling the hair bundle amplification in birds and other non-mammalian species. Control of the bundle motor by the efferent system presents a challenge to hypotheses that attribute cochlear amplification to the MET molecular apparatus because a clear mechanism for fast control via
efferent synaptic input is unclear. In contrast, the power output of flexoelectric stereocilia described here is controlled by the electrical admittance of the hair cell soma, a parameter modulated by the efferent system 
. In the present theoretical analysis, the power output at best frequency drops substantially when the somatic impedance is reduced. This occurs because the input MET power is lost to ground instead of being utilized to drive the flexoelectric hair bundle motor. Thus, hair bundle flexoelectric power output could be controlled by efferent modulation of somatic impedance.
It has been argued previously that active hair bundle movements may underlie the exquisite sensitivity and frequency selectivity of hearing, particularly in non-mammalian species that do not express prestin-mediated somatic motility 
. Indeed, a negative bundle “twitch”
has been measured in hair bundles consistent with flexoelectric powered bundle movements (). Furthermore, the model predicts 200 aW of bundle power for a typical transduction current of 100 pA (2 aW/pA at 1 kHz), which compares favorably with a measured power output of 79 aW (79 zJ bundle work per cycle) 
. In previous work, biophysics of the motor(s) has been closely associated with aspects of the MET complex
but it has also been shown that voltage clamp of the hair cell soma evokes a very fast negative hair-bundle displacement even when the MET channels are completely blocked 
. These voltage-dependent bundle movements augment motor actions associated with the MET apparatus and are consistent with the flexoelectric based bundle movements described here. Nevertheless, it has not yet been directly proven that flexoelectricity underlies the voltage-dependent responses in hair bundles and additional experiments will be necessary to test this hypothesis. The most direct experiments would involve investigations of axial force generation and/or membrane tension changes in individual stereocilia under somatic voltage clamp conditions with the MET channels blocked. Cholesterol and other compounds are known to influence the flexoelectric coefficient of membranes and thereby could be used to manipulate the force and displacement. Similar experiments could be done for transverse vs. axial motion comparing wild type to model organisms such as the myosin-XVa mutant lacking a staircase architecture. Manipulation of the actin core and protein accessory structure to modify axial and bending stiffness could also be revealing. Interestingly, the model suggests that as the cell is hyperpolarized, depending upon axial stiffness, there may be a critical voltage where the microvilli becomes unstable and suddenly bends in a way analogous to buckling of an axially loaded column.
Under physiological conditions, the flexoelectric motor would be powered by the MET current and thereby reflective of adaptations and temporal features of the MET molecular complex. Being independent of ATP and drawing from the large electro-chemical potential energy store of the inner ear endolymph fluid, the flexoelectric motor has great advantages of high speed and large power output over more conventional biological motors. Results suggest that the flexoelectric motor may generate the power-stroke of hair bundle motility (), at least at high frequencies above ~200 Hz where ATPase would be too slow to operate on a cycle-by-cycle basis. Although our flexoelectric efficiency analysis is linear, interplay between MET current kinetics, bundle movements and flexoelectricity would be expected to introduce a nonlinearity consistent with spontaneous bundle oscillations. This interplay might underlie a limit cycle and Hopf
bifurcation that has been observed experimentally, and may be linked to the exquisite sensitivity of hearing 
. Flexoelectricity also provides a simple explanation that, when thought of in terms of the efficiency of electrical to mechanical power conversion, proves adequate to predict the height of individual stereocilia as a function of cell best frequency and thus presents a universal explanation for the amazing tonotopic organization expressed in the cochlea.