Fast adaptation of cooperative channels engenders Hopf bifurcations in auditory hair cells

Gianoli, Francesco; Hogan, Brenna; Dilly, Émilien; Risler, Thomas; Kozlov, Andrei S.

doi:10.1016/j.bpj.2022.02.016

Cited by 3 publications

(1 citation statement)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rightmost of Fig. 3 shows that 1 hr post-stimulation cells have not fully recovered the original morphology because the healing process takes longer [ 64 , 65 ]. Although blebs were traditionally viewed as a sign of apoptosis, there is an increasing body of evidence supporting their active role in cell motility and spreading [ 66 ], mitosis [ 55 ], and endocytosis [ 67 ].…”

Section: Resultsmentioning

confidence: 99%

Vibropolyfection: coupling polymer-mediated gene delivery to mechanical stimulation to enhance transfection of adherent cells

et al. 2022

View full text Add to dashboard Cite

Background With the success of recent non-viral gene delivery-based COVID-19 vaccines, nanovectors have gained some public acceptance and come to the forefront of advanced therapies. Unfortunately, the relatively low ability of the vectors to overcome cellular barriers adversely affects their effectiveness. Scientists have thus been striving to develop ever more effective gene delivery vectors, but the results are still far from satisfactory. Therefore, developing novel strategies is probably the only way forward to bring about genuine change. Herein, we devise a brand-new gene delivery strategy to boost dramatically the transfection efficiency of two gold standard nucleic acid (NA)/polymer nanoparticles (polyplexes) in vitro. Results We conceived a device to generate milli-to-nanoscale vibrational cues as a function of the frequency set, and deliver vertical uniaxial displacements to adherent cells in culture. A short-lived high-frequency vibrational load (t = 5 min, f = 1,000 Hz) caused abrupt and extensive plasmalemma outgrowths but was safe for cells as neither cell proliferation rate nor viability was affected. Cells took about 1 hr to revert to quasi-naïve morphology through plasma membrane remodeling. In turn, this eventually triggered the mechano-activated clathrin-mediated endocytic pathway and made cells more apt to internalize polyplexes, resulting in transfection efficiencies increased from 10-to-100-fold. Noteworthy, these results were obtained transfecting three cell lines and hard-to-transfect primary cells. Conclusions In this work, we focus on a new technology to enhance the intracellular delivery of NAs and improve the transfection efficiency of non-viral vectors through priming adherent cells with a short vibrational stimulation. This study paves the way for capitalizing on physical cell stimulation(s) to significantly raise the effectiveness of gene delivery vectors in vitro and ex vivo. Graphical Abstract

show abstract

Section: Resultsmentioning

confidence: 99%

Vibropolyfection: coupling polymer-mediated gene delivery to mechanical stimulation to enhance transfection of adherent cells

et al. 2022

View full text Add to dashboard Cite

show abstract

Auditory Cellular Cooperativity Probed Via Spontaneous Otoacoustic Emissions

Bergevin,

Whiley,

Wit

et al. 2024

Preprint

View full text Add to dashboard Cite

As a sound pressure detector that uses energy to boost both its sensitivity and selectivity, the inner ear is an active non-equilibrium system. The collective processes of the inner ear giving rise to this exquisite functionality remain poorly understood. One manifestation of the active ear across the animal kingdom is the presence of spontaneous otoacoustic emission (SOAE), idiosyncratic arrays of spectral peaks that can be measured using a sensitive microphone in the ear canal.1 Current SOAE models attempt to explain how multiple peaks arise, and generally assume a spatially-distributed tonotopic system. However, the nature of the generators, their coupling, and the role of noise (e.g., Brownian motion) are hotly debated, especially given the inner ear morphological diversity across vertebrates. One means of probing these facets of emission generation is studying fluctuations in SOAE peak properties, which produce amplitude (AM) and frequency modulations (FM). These properties are likely related to the presence of noise affecting active cellular generation elements, and the coupling between generators. To better biophysically constrain models, this study characterizes the fluctuations in filtered SOAE peak waveforms, focusing on interrelations within and across peaks. A systematic approach is taken, examining three species that exhibit disparate inner ear morphologies: humans, barn owls, and green anole lizards. To varying degrees across all three groups, SOAE peaks have intra-(IrP) and interpeak (IPP) correlations indicative of interactions between generative elements. Activity from anole lizards, whose auditory sensory organ is relatively much smaller than that of humans or barn owls, showed a much higher incidence of IPP correlations. Taken together, we propose that these data are indicative of SOAE cellular generators acting cooperatively, allowing the ear to function as an optimized detector.Significance StatementThe inner ear is a complex biomechanical system whose function is not well understood. To further elucidate the role of coupling in emission generation, this study systematically compares fluctuations in sound emitted spontaneously from the ear (spontaneous otoacoustic emission, SOAE) across three vertebrates. Ultimately these data serve to illustrate that the inner ear is a non-equilibrium, active system whose cellular elements work cooperatively. A clearer understanding of SOAE generation and how it manifests across the animal kingdom will significantly advance our understanding of both normal and impaired auditory function.

show abstract

Dynamic modulation of auditory hair cell stereocilia membrane mechanics by the scrambling mechanotransduction complex

George,

Ricci

2024

Preprint

View full text Add to dashboard Cite

Inner ear sensory hair cells convert mechanical deflection of their hair bundle into an electrical signal by gating novel mechanoelectrical transduction (MET) channels. Transmembrane channel-like proteins (TMCs) are a component of the MET machinery and part of a superfamily of molecules whose members are ion channels or lipid scramblases. As the stereocilia membrane modulates MET channels properties and the stereocilia membrane has different properties than the soma, we investigated the potential scramblase activity of the MET machinery using a novel viscosity sensor BODIPY 1c. Developmental, genetic, electrophysiological and pharmacological data demonstrate that both TMC1 and TMC2 are mechanosensitive scramblases as activity depends on MET channel being open. Blockage of scramblase activity unmasks a second process that increases effective membrane viscosity independent of MET machinery. Together our data reveal a dynamic regulation of stereocilia membrane that may underlie the speed and sensitivity of the MET process.

show abstract

Fast adaptation of cooperative channels engenders Hopf bifurcations in auditory hair cells

Cited by 3 publications

References 54 publications

Vibropolyfection: coupling polymer-mediated gene delivery to mechanical stimulation to enhance transfection of adherent cells

Vibropolyfection: coupling polymer-mediated gene delivery to mechanical stimulation to enhance transfection of adherent cells

Auditory Cellular Cooperativity Probed Via Spontaneous Otoacoustic Emissions

Dynamic modulation of auditory hair cell stereocilia membrane mechanics by the scrambling mechanotransduction complex

Contact Info

Product

Resources

About