Hair Cell Bundles: Flexoelectric Motors of the Inner Ear

Microvilli (stereocilia) projecting from the apex of hair cells in the inner ear are actively motile structures that feed energy into the vibration of the inner ear and enhance sensitivity to sound. The biophysical mechanism underlying the hair bundle motor is unknown. In this study, we examined a membrane flexoelectric origin for active movements in stereocilia and conclude that it is likely to be an important contributor to mechanical power output by hair bundles. We formulated a realistic biophysical model of stereocilia incorporating stereocilia dimensions, the known flexoelectric coefficient of lipid membranes, mechanical compliance, and fluid drag. Electrical power enters the stereocilia through displacement sensitive ion channels and, due to the small diameter of stereocilia, is converted to useful mechanical power output by flexoelectricity. This motor augments molecular motors associated with the mechanosensitive apparatus itself that have been described previously. The model reveals stereocilia to be highly efficient and fast flexoelectric motors that capture the energy in the extracellular electro-chemical potential of the inner ear to generate mechanical power output. The power analysis provides an explanation for the correlation between stereocilia height and the tonotopic organization of hearing organs. Further, results suggest that flexoelectricity may be essential to the exquisite sensitivity and frequency selectivity of non-mammalian hearing organs at high auditory frequencies, and may contribute to the “cochlear amplifier” in mammals

Structure and Function of Negri Bodies

Replication and assembly of many viruses occur in viral factories which are specialized intracellular compartments formed during viral infection. For rabies virus, those viral factories are called Negri bodies (NBs). NBs are cytoplasmic inclusion bodies in which viral RNAs (mRNAs as well as genomic and antigenomic RNAs) are synthesized. NBs are spherical, they can fuse together, and can reversibly deform when encountering a physical barrier. All these characteristics are similar to those of eukaryotic membrane-less liquid organelles which contribute to the compartmentalization of the cell interior. Indeed, the liquid nature of NBs has been confirmed by FRAP experiments. The co-expression of rabies virus nucleoprotein N and phosphoprotein P is sufficient to induce the formation of cytoplasmic inclusions recapitulating NBs properties. Remarkably, P and N have features similar to those of cellular proteins involved in liquid organelles formation: N is an RNA-binding protein and P contains intrinsically disordered domains. An overview of the literature indicates that formation of liquid viral factories by phase separation is probably common among Mononegavirales. This allows specific recruitment and concentration of viral proteins. Finally, as virus-associated molecular patterns recognized by cellular sensors of RNA virus replication are probably essentially present in the viral factory, there should be a subtle interplay (which remains to be characterized) between those liquid structures and the cellular proteins which trigger the innate immune response