Src- and confinement-dependent FAK activation causes E-cadherin relaxation and β-catenin activity

Gayrard, Charlène; Bernaudin, Clément; Déjardin, Théophile; Seiler, Cynthia; Borghi, Nicolas

doi:10.1083/jcb.201706013

Cited by 61 publications

(92 citation statements)

References 64 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We observed the preferential loss of β-catenin from E-cadherin junctions within the localized regions of high celladhesion tension 24 hours following BMP4 stimulation ( Figure 6A). Activated phospho-Srcfamily kinases (pSFKs) phosphorylate junctional β-catenin to facilitate its release from adherens junction complexes (Bienz, 2005;Gayrard et al, 2018;Gottardi and Gumbiner, 2004;Howard et al, 2011;Lilien and Balsamo, 2005;Laralynne Przybyla et al, 2016). Consistently, we detected high levels of pSFKs within 6 hours of BMP4 stimulation, specifically within regions of high celladhesion tension ( Figure 6B).…”

Section: High Cell Tension Promotes β-Catenin Release From Adherens Jsupporting

confidence: 65%

Mechanics regulate human embryonic stem cell self-organization to specify mesoderm

Muncie

Ayad

Lakins

et al. 2020

Preprint

View full text Add to dashboard Cite

Embryogenesis is directed by morphogens that induce differentiation within a defined tissue geometry. Tissue organization is mediated by cell-cell and cell-extracellular matrix (ECM) adhesions and is modulated by cell tension and tissue-level force. Whether cell tension regulates development by directly influencing morphogen signaling remains unclear. Human embryonic stem cells (hESCs) exhibit an intrinsic capacity for self-organization that motivates their use as a tractable model of early human embryogenesis. We engineered patterned substrates that enhance cell-cell interactions to direct the self-organization of cultured hESCs into "gastrulation-like" nodes. Tissue geometries that generate local nodes of high cell-cell tension and induce these selforganized tissue nodes drive BMP4-dependent gastrulation by enhancing phosphorylation and nuclear translocation of β-catenin to promote Wnt signaling and mesoderm specification. The findings underscore the interplay between tissue organization, cell tension, and morphogendependent differentiation, and demonstrate that cell-and tissue-level forces directly regulate cell fate specification in early human development.

show abstract

Section: High Cell Tension Promotes β-Catenin Release From Adherens Jsupporting

confidence: 65%

Mechanics regulate human embryonic stem cell self-organization to specify mesoderm

Muncie

Ayad

Lakins

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…5c). Overall, these observations are in good agreement with some previous studies on the global force distributions during this process 17,36,61 .…”

Section: Dynamics Of E-cadherin-mediated Tensionsupporting

confidence: 93%

Quantifying Tensile Forces at Cell–Cell Junctions with a DNA-based Fluorescent Probe

Zhao

Xie

et al. 2020

Preprint

View full text Add to dashboard Cite

Cells are physically contacting with each other. Direct and precise quantification of forces at cell-cell junctions is still challenging. Herein, we have developed a DNA-based ratiometric fluorescent probe, termed DNAMeter, to quantify intercellular tensile forces. These lipidmodified DNAMeters can spontaneously anchor onto live cell membranes. The DNAMeter consists of two self-assembled DNA hairpins of different force tolerance. Once the intercellular tension exceeds the force tolerance to unfold a DNA hairpin, a specific fluorescence signal will be activated, which enables the real-time imaging and quantification of tensile forces. Using Ecadherin-modified DNAMeter as an example, we have demonstrated an approach to quantify, at the molecular level, the magnitude and distribution of E-cadherin tension among epithelial cells.Compatible with readily accessible fluorescence microscopes, these easy-to-use DNA tension probes can be broadly used to quantify mechanotransduction in collective cell behaviors.

show abstract

“…In recent FRET‐based tension sensor studies , sample sizes have ranged from tens to hundreds, and statistics have been done on data that varies in length scale from subcellular structures to whole cells. Therefore, we investigated how sample size, specifically the number of cells analyzed, affects the uncertainty of FRET efficiency measurements.…”

Section: Resultsmentioning

confidence: 99%

Improving Quality, Reproducibility, and Usability of FRET‐Based Tension Sensors

et al. 2018

View full text Add to dashboard Cite

Mechanobiology, the study of how mechanical forces affect cellular behavior, is an emerging field of study that has garnered broad and significant interest. Researchers are currently seeking to better understand how mechanical signals are transmitted, detected, and integrated at a subcellular level. One tool for addressing these questions is a Förster resonance energy transfer (FRET)‐based tension sensor, which enables the measurement of molecular‐scale forces across proteins based on changes in emitted light. However, the reliability and reproducibility of measurements made with these sensors has not been thoroughly examined. To address these concerns, we developed numerical methods that improve the accuracy of measurements made using sensitized emission‐based imaging. To establish that FRET‐based tension sensors are versatile tools that provide consistent measurements, we used these methods, and demonstrated that a vinculin tension sensor is unperturbed by cell fixation, permeabilization, and immunolabeling. This suggests FRET‐based tension sensors could be coupled with a variety of immuno‐fluorescent labeling techniques. Additionally, as tension sensors are frequently employed in complex biological samples where large experimental repeats may be challenging, we examined how sample size affects the uncertainty of FRET measurements. In total, this work establishes guidelines to improve FRET‐based tension sensor measurements, validate novel implementations of these sensors, and ensure that results are precise and reproducible. © 2018 International Society for Advancement of Cytometry

show abstract

Src- and confinement-dependent FAK activation causes E-cadherin relaxation and β-catenin activity

Cited by 61 publications

References 64 publications

Mechanics regulate human embryonic stem cell self-organization to specify mesoderm

Mechanics regulate human embryonic stem cell self-organization to specify mesoderm

Quantifying Tensile Forces at Cell–Cell Junctions with a DNA-based Fluorescent Probe

Improving Quality, Reproducibility, and Usability of FRET‐Based Tension Sensors

Contact Info

Product

Resources

About