Visualizing the building blocks of cell-cell adhesion
Scientists at the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) have discovered the molecular mechanisms responsible for the formation of the adherens junction at the nanoscale level. This research is published in Developmental Cell (Wu et al., Actin-delimited adhesion-independent clustering of E-cadherin forms the nanoscale building blocks of adherens junctions, Developmental Cell, 16 Jan 2015, doi.org/10.1016/j.devcel.2014.12.003).
Mechanobiology Institute, National University of Singapore
Figure: Superresolution imaging of E-cadherin at the cell membrane. Conventional microscopy (white box) shows E-cadherin as a belt along the cell membrane. Superresolution imaging reveals that E-cadherin assembles as distinct, punctate clusters. Detailed imaging at the nanoscale level demonstrates that these clusters do not merge (dotted red box).
How are cell-cell adhesions initiated?
Although the cells that make up our body are functional units by themselves, they need to interact with each other and their environment to fulfill all their functions. Cells stick to one another as well as to their substrate through physical contacts called cell adhesions. Apart from serving as physical connections that enable cells to form tissues, cell adhesions also allow the cells to sense, signal, and respond to physical or chemical changes in the environment, as well as interact with neighbouring cells.
This is, at least in part, due to the structure of adhesion sites, or cell-cell junctions, which extend through the cell surface into the cell’s interior. At cell-cell junctions, adhesion receptors at the cell surface are linked via adaptor proteins to the cytoskeleton, a structural scaffold inside the cell composed of filamentous proteins like actin. Epithelial cadherin (E-cadherin) is a major adhesion receptor protein which forms a prominent cell-cell adhesion complex called the adherens junction.
Traditionally it was thought that clusters of E-cadherin merge to form a thick belt along the cell membrane between adjacent cells. The binding of individual E-cadherin proteins was thought to drive adhesion, with clusters formed in an adhesion-dependent manner, before merging and becoming uniformly distributed over time. This has long been the prevalent notion, based on conventional microscopy, which is limited in its ability to clearly visualize structures as small as the adherens junction or E-cadherin cluster.
However, recent findings by MBI researchers disprove this notion. Using a combination of an advanced imaging technique called superresolution microscopy along with quantitative analysis and mutational studies, MBI Principal Investigators Associate Professor Ronen Zaidel-Bar and Associate Professor Pakorn Kanchanawong and graduate student Yao Wu show that cell-cell adhesions are initiated by small clusters of about five E-cadherin molecules. Superresolution imaging allowed the nanoscale architecture of the adherens junction to be observed, and distinct, evenly sized E-cadherin clusters were monitored both in the incipient and mature cell-cell adhesions. The precursor E-cadherin cluster forms independently of adhesion, even when mutations prevent E-cadherin interactions, indicating that their formation relies on an alternative mechanism.
As more E-cadherin molecules were recruited from neighbouring cells, the clusters became denser especially at their core. However, E-cadherin clusters never increased in size or merged to form the hypothesized belt. Instead, the actin cytoskeleton was seen to fence E-cadherin clusters, thereby preventing them from merging.
These newly identified steps of adherens junction assembly, organization and maintenance advance our understanding of how adherens junctions adapt to dynamic changes in the behaviour of epithelial cells. Regulating essential functions such as cell shape, movement and rearrangement is vital for maintaining epithelium integrity, and is also important for tissue repair in wound healing and disease.
Phone: +65 6516 5125
Amal Naquiah | newswise
A human liver cell atlas
15.07.2019 | Max Planck Institute of Immunobiology and Epigenetics
Researchers reveal mechanisms for regulating temperature sensitivity of soil organic matter decompos
15.07.2019 | Chinese Academy of Sciences Headquarters
For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.
Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...
An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".
The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...
An interdisciplinary research team at the Technical University of Munich (TUM) has built platinum nanoparticles for catalysis in fuel cells: The new size-optimized catalysts are twice as good as the best process commercially available today.
Fuel cells may well replace batteries as the power source for electric cars. They consume hydrogen, a gas which could be produced for example using surplus...
The fly agaric with its red hat is perhaps the most evocative of the diverse and variously colored mushroom species. Hitherto, the purpose of these colors was...
Physicists at the Max Planck Institute for Nuclear Physics in Heidelberg report the first result of the new Alphatrap experiment. They measured the bound-electron g-factor of highly charged (boron-like) argon ions with unprecedented precision of 9 digits. In comparison with a new highly accurate quantum electrodynamic calculation they found an excellent agreement on a level of 7 digits. This paves the way for sensitive tests of QED in strong fields like precision measurements of the fine structure constant α as well as the detection of possible signatures of new physics. [Physical Review Letters, 27 June 2019]
Quantum electrodynamics (QED) describes the interaction of charged particles with electromagnetic fields and is the most precisely tested physical theory. It...
24.06.2019 | Event News
29.04.2019 | Event News
17.04.2019 | Event News
15.07.2019 | Life Sciences
15.07.2019 | Power and Electrical Engineering
15.07.2019 | Life Sciences