The closest look ever at native human tissue

December 5, 2007
The closest look ever at native human tissue
This 3-D reconstruction of a human skin cell was produced by electron tomography and shows organelles in different colours: regions of cell-cell contact (sandy brown), nucleus and nuclear envelope (blue) with pores (red), microtubules (green), mitochondria (purple), endoplasmic reticulum (steel blue). Credit: Achilleas Frangakis EMBL

Seeing proteins in their natural environment and interactions inside cells has been a long-standing goal. Using an advanced microscopy technique called cryo-electron tomography, researchers from the European Molecular Biology Laboratory [EMBL] have visualised proteins responsible for cell-cell contacts for the first time. In this week’s issue of Nature they publish the first 3D image of human skin at molecular resolution and reveal the molecular Velcro-like organisation that interlinks cells.

“This is a real breakthrough in two respects,” says Achilleas Frangakis, group leader at EMBL. “Never before has it been possible to look in three dimensions at a tissue so close to its native state at such a high resolution. We can now see details at the scale of a few millionths of a millimetre. In this way we have gained a new view on the interactions of molecules that underlie cell adhesion in tissues – a mechanism that has been disputed over decades.”

So far, the only information available about a protein’s position and interactions in a cell was based on either light microscopy images at poor resolution or techniques that remove proteins from their natural context. Frangakis and his group have been developing a technique called cryo-electron tomography, with which a cell or tissue is instantly frozen in its natural state and then examined with an electron micro-scope. Electron microscopy normally requires tissue to be treated with chemicals or coated in metal, a procedure that disturbs the natural state of a sample. With cyro-electron tomography, images are taken of the untreated sample from different directions and assembled into an accurate 3D image by a computer.

The researchers applied this technique to observe proteins that are crucial for the integrity of tissues and organs like the skin and the heart, but also play an important role in cell proliferation. These proteins, called cadherins, are anchored in cell membranes and interact with each other to bring cells close together and interlink them tightly.

“We could see the interaction between two cadherins directly, and this revealed where the strength of human skin comes from,” says Ashraf Al-Amoudi, who carried out the work in Frangakis’ lab. “The trick is that each cadherin binds twice: once to a molecule from the juxtaposed cell, and once to its next-door neighbour. The system works a bit like specialised Velcro and establishes very tight contacts between cells.”

The new insights into the cadherin system broadens the understanding of structural aspects of cell adhesion and shed light on other crucial processes such as cell proliferation. The technical advances achieved in cryo-electron tomography of frozen sections open up new possibilities to study more systems at native conditions with molecular resolution.

Source: European Molecular Biology Laboratory

Explore further: The regulation of meiotic crossover in plants

Related Stories

Key protein in cilia assembly identified

August 21, 2015

The group led by ICREA Research Professor Cayetano Gonzalez at IRB Barcelona, in collaboration with the group of Professor Giuliano Callaini from the University of Siena in Italy, has published a new study in Current Biology ...

Molecular machine, not assembly line, assembles microtubules

August 20, 2015

When they think about how cells put together the molecules that make life work, biologists have tended to think of assembly lines: Add A to B, tack on C, and so on. But the reality might be more like a molecular version of ...

FIC proteins send bacteria into hibernation

August 20, 2015

Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue ...

Team identifies structure of tumor-suppressing protein

August 20, 2015

An international group of researchers led by Carnegie Mellon University physicists Mathias Lösche and Frank Heinrich have established the structure of an important tumor suppressing protein, PTEN. Their findings provide ...

Recommended for you

Male seahorse and human pregnancies remarkably alike

September 1, 2015

Their pregnancies are carried by the males but, when it comes to breeding, seahorses have more in common with humans than previously thought, new research from the University of Sydney reveals.

Brazilian wasp venom kills cancer cells by opening them up

September 1, 2015

The social wasp Polybia paulista protects itself against predators by producing venom known to contain a powerful cancer-fighting ingredient. A Biophysical Journal study published September 1 reveals exactly how the venom's ...

ATLAS and CMS experiments shed light on Higgs properties

September 1, 2015

Three years after the announcement of the discovery of a new particle, the so-called Higgs boson, the ATLAS and CMS Collaborations present for the first time combined measurements of many of its properties, at the third annual ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.