Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Sensing sound: Cellular specializations and molecular force sensors.

ABSTRACT: Organisms of all phyla express mechanosensitive ion channels with a wide range of physiological functions. In recent years, several classes of mechanically gated ion channels have been identified. Some of these ion channels are intrinsically mechanosensitive. Others depend on accessory proteins to regulate their response to mechanical force. The mechanotransduction machinery of cochlear hair cells provides a particularly striking example of a complex force-sensing machine. This molecular ensemble is embedded into a specialized cellular compartment that is crucial for its function. Notably, mechanotransduction channels of cochlear hair cells are not only critical for auditory perception. They also shape their cellular environment and regulate the development of auditory circuitry. Here, we summarize recent discoveries that have shed light on the composition of the mechanotransduction machinery of cochlear hair cells and how this machinery contributes to the development and function of the auditory system.

SUBMITTER: Qiu X

PROVIDER: S-EPMC9671866 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Sensing sound: Cellular specializations and molecular force sensors.

Qiu Xufeng X Müller Ulrich U

Neuron 20221011 22

Organisms of all phyla express mechanosensitive ion channels with a wide range of physiological functions. In recent years, several classes of mechanically gated ion channels have been identified. Some of these ion channels are intrinsically mechanosensitive. Others depend on accessory proteins to regulate their response to mechanical force. The mechanotransduction machinery of cochlear hair cells provides a particularly striking example of a complex force-sensing machine. This molecular ensembl ...[more]

PMID: 36223766

Similar Datasets

Cellular force-sensing through actin filaments.

Project description:The actin cytoskeleton orchestrates cell mechanics and facilitates the physical integration of cells into tissues, while tissue-scale forces and extracellular rigidity in turn govern cell behaviour. Here, we discuss recent evidence that actin filaments (F-actin), the core building blocks of the actin cytoskeleton, also serve as molecular force sensors. We delineate two classes of proteins, which interpret forces applied to F-actin through enhanced binding interactions: 'mechanically tuned' canonical actin-binding proteins, whose constitutive F-actin affinity is increased by force, and 'mechanically switched' proteins, which bind F-actin only in the presence of force. We speculate mechanically tuned and mechanically switched actin-binding proteins are biophysically suitable for coordinating cytoskeletal force-feedback and mechanical signalling processes, respectively. Finally, we discuss potential mechanisms mediating force-activated actin binding, which likely occurs both through the structural remodelling of F-actin itself and geometric rearrangements of higher-order actin networks. Understanding the interplay of these mechanisms will enable the dissection of force-activated actin binding's specific biological functions.

| S-EPMC9945651 | biostudies-literature

Structural specializations of A2, a force-sensing domain in the ultralarge vascular protein von Willebrand factor.

Project description:The lengths of von Willebrand factor (VWF) concatamers correlate with hemostatic potency. After secretion in plasma, length is regulated by hydrodynamic shear force-dependent unfolding of the A2 domain, which is then cleaved by a specific protease. The 1.9-A crystal structure of the A2 domain demonstrates evolutionary adaptations to this shear sensor function. Unique among VWF A (VWA) domains, A2 contains a loop in place of the alpha4 helix, and a cis-proline. The central beta4-strand is poorly packed, with multiple side-chain rotamers. The Tyr-Met cleavage site is buried in the beta4-strand in the central hydrophobic core, and the Tyr structurally links to the C-terminal alpha6-helix. The alpha6-helix ends in 2 Cys residues that are linked by an unusual vicinal disulfide bond that is buried in a hydrophobic pocket. These features may narrow the force range over which unfolding occurs and may also slow refolding. Von Willebrand disease mutations, which presumably lower the force at which A2 unfolds, are illuminated by the structure.

| S-EPMC2695068 | biostudies-literature

Quantifying Molecular Forces with Serially Connected Force Sensors.

Project description:To understand the mechanical forces involved in cell adhesion, molecular force sensors have been developed to study tension through adhesion proteins. Recently, a class of molecular force sensors called tension gauge tethers (TGTs) have been developed that rely on irreversible force-dependent dissociation of a DNA duplex to study cell adhesion forces. Although the TGT offers a high signal-to-noise ratio and is ideal for studying fast/single-molecular adhesion processes, quantitative interpretation of experimental results has been challenging. Here, we use a computational approach to investigate how TGT fluorescence readout can be quantitatively interpreted. In particular, we studied force sensors made of a single TGT, multiplexed single TGTs, and two TGTs connected in series. Our results showed that fluorescence readout using a single TGT can result from drastically different combinations of force history and adhesion event density that span orders of magnitude. In addition, the apparent behavior of the TGT is influenced by the tethered receptor-ligand, making it necessary to calibrate the TGT with every new receptor-ligand. To solve this problem, we proposed a system of two serially connected TGTs. Our result shows that not only is the ratiometric readout of serial TGT independent of the choice of receptor-ligand, it is able to reconstruct force history with sub-pN force resolution. This is also not possible by simply multiplexing different types of TGTs together. Last, we systematically investigated how the sequence composition of the two serially connected TGTs can be tuned to achieve different dynamic range. This computational study demonstrated how serially connected irreversible molecular dissociation processes can accurately quantify molecular force and laid the foundation for subsequent experimental studies.

| S-EPMC6451047 | biostudies-literature

Molecular and cellular changes underlying evolutionary specializations of primate dorsolateral prefrontal cortex

Project description:The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. Here, we assessed over 600,000 single-nucleus transcriptomes from human, chimpanzee, macaque, and marmoset dlPFC. While major subclasses of transcriptomically-defined cell subtypes are conserved, we detected several subtypes only in some species and substantial species-specific molecular differences across homologous neuronal, glial and non-neural subtypes. The latter are exemplified by human-specific switching between translation of the neuropeptide somatostatin (SST) and tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine production, in certain interneurons, and also by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer-4 granular neurons. We generated a comprehensive transcriptomic and cellular survey of dlPFC evolution in anthropoid primates.

2022-08-25 | GSE206994 | GEO

Molecular logic for cellular specializations that initiate the auditory parallel processing pathways

Project description:The cochlear nuclear complex (CN), the starting point for all central auditory processing, comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals, yet molecular logic governing cellular specializations remains largely unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple new subtypes with anatomical and physiological identity. The resulting complete cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling determination of molecular basis of the remarkable cellular phenotypes in the CN. In particular, CN cell-type identity is encoded in a transcriptional architecture that orchestrates functionally congruent expression across a small set of gene families to customize projection patterns, input-output synaptic communication, and biophysical features required for encoding distinct aspects of acoustic signals. This high-resolution account of cellular heterogeneity from the molecular to the circuit level illustrates molecular logic for cellular specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.

2024-11-04 | GSE273145 | GEO

Flexible mechanical metamaterials enabling soft tactile sensors with multiple sensitivities at multiple force sensing ranges.

Project description:The majority of existing tactile sensors are designed to measure a particular range of force with a fixed sensitivity. However, some applications require tactile sensors with multiple task-relevant sensitivities at multiple ranges of force sensing. Inspired by the human tactile sensing capability, this paper proposes a novel soft tactile sensor based on mechanical metamaterials which exhibits multiple sensitivity regimes due to the step-by-step locking behaviour of its heterogenous multi-layered structure. By tuning the geometrical design parameters of the collapsible layers, each layer experiences locking behaviour under different ranges of force which provides different sensitivity of the sensor at different force magnitude. The integration of a magnetic-based transduction method with the proposed structure results in high design degrees of freedom for realising the desired contact force sensitivities and corresponding force sensing ranges. A systematic design procedure is proposed to select appropriate design parameters to produce the desired characteristics. Two example designs of the sensor structure were fabricated using widely available benchtop 3D printers and tested for their performance. The results showed the capability of the sensor in providing the desired characteristics in terms of sensitivity and force range and being realised in different shapes, sizes and number of layers in a single structure. The proposed multi-sensitivity soft tactile sensor has a great potential to be used in a wide variety of applications where different sensitivities of force measurement is required at different ranges of force magnitudes, from robotic manipulation and human-machine interaction to biomedical engineering and health-monitoring.

| S-EPMC8677735 | biostudies-literature

Molecular and cellular changes underlying evolutionary specializations of primate dorsolateral prefrontal cortex II

2022-08-25 | GSE207334 | GEO

Restriction of receptor movement alters cellular response: physical force sensing by EphA2.

Project description:Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitative analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.

| S-EPMC2895569 | biostudies-literature

Shielded soft force sensors.

Project description:Force and strain sensors made of soft materials enable robots to interact intelligently with their surroundings. Capacitive sensing is widely adopted thanks to its low power consumption, fast response, and facile fabrication. Capacitive sensors are, however, susceptible to electromagnetic interference and proximity effects and thus require electrical shielding. Shielding has not been previously implemented in soft capacitive sensors due to the parasitic capacitance between the shield and sensing electrodes, which changes when the sensor is deformed. We address this crucial challenge by patterning the central sensing elastomer layer to control its compressibility. One design uses an ultrasoft silicone foam, and the other includes microchannels filled with liquid metal and air. The force resolution is sub-mN both in normal and shear directions, yet the sensor withstands large forces (>20 N), demonstrating a wide dynamic range. Performance is unaffected by nearby high DC and AC electric fields and even electric sparks.

| S-EPMC9363457 | biostudies-literature

Nanoscale Cellular Traction Force Quantification: CRISPR-Cas12a Supercharged DNA Tension Sensors in Nanoclustered Ligand Patterns.

Project description:High-throughput measurement of cellular traction forces at the nanoscale remains a significant challenge in mechanobiology, limiting our understanding of how cells interact with their microenvironment. Here, we present a novel technique for fabricating protein nanopatterns in standard multiwell microplate formats (96/384-wells), enabling the high-throughput quantification of cellular forces using DNA tension gauge tethers (TGTs) amplified by CRISPR-Cas12a. Our method employs sparse colloidal lithography to create nanopatterned surfaces with feature sizes ranging from sub 100 to 800 nm on transparent, planar, and fully PEGylated substrates. These surfaces allow for the orthogonal immobilization of two different proteins or biomolecules using click-chemistry, providing precise spatial control over cellular signaling cues. We demonstrate the robustness and versatility of this platform through imaging techniques, including total internal reflection fluorescence microscopy, confocal laser scanning microscopy, and high-throughput imaging. Applying this technology, we measured the early stage mechanical forces exerted by 3T3 fibroblasts across different nanoscale features, detecting forces ranging from 12 to 56 pN. By integrating the Mechano-Cas12a Assisted Tension Sensor (MCATS) system, we achieved rapid and high-throughput quantification of cellular traction forces, analyzing over 2 million cells within minutes. Our findings reveal that nanoscale clustering of integrin ligands significantly influences the mechanical responses of cells. This platform offers a powerful tool for mechanobiology research, facilitating the study of cellular forces and mechanotransduction pathways in a high-throughput manner compatible with standard cell culture systems.

| S-EPMC11803557 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data