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: Research shows that circular RNAs, until now considered non-coding, can encode for proteins

Related Stories

How protein modifications influence apoptosis

March 21, 2017

Researchers at the Lomonosov Moscow State University have described the molecular mechanisms of post-translational modifications of caspases, a family of proteolytic enzymes, and how they function during apoptosis, the process ...

In a sample of blood, researchers probe for cancer clues

March 24, 2017

One day, patients may be able to monitor their body's response to cancer therapy just by having their blood drawn. A new study, led by bioengineers at UC Berkeley, has taken an important step in that direction by measuring ...

Big data approach to predict protein structure

March 24, 2017

Nothing works without proteins in the body, they are the molecular all-rounders in our cells. If they do not work properly, severe diseases, such as Alzheimer's, may result. To develop methods to repair malfunctioning proteins, ...

Manipulating plant enzymes could protect crops from flooding

March 24, 2017

Scientists have long understood how oxygen deprivation can affect animals and even bacteria, but until recently very little was known about how plants react to hypoxia (low oxygen). A new research collaboration between Oxford ...

Recommended for you

Planetary waves, first found on Earth, are discovered on Sun

March 27, 2017

The same kind of large-scale planetary waves that meander through the atmosphere high above Earth's surface may also exist on the Sun, according to a new study led by a scientist at the National Center for Atmospheric Research ...

Stars born in winds from supermassive black holes

March 27, 2017

Observations using ESO's Very Large Telescope have revealed stars forming within powerful outflows of material blasted out from supermassive black holes at the cores of galaxies. These are the first confirmed observations ...

Farming becoming riskier under climate change

March 27, 2017

Scientists the world over are working to predict how climate change will affect our planet. It is an extremely complex puzzle with many moving parts, but a few patterns have been consistent, including the prediction that ...

NASA spacecraft investigate clues in radiation belts

March 27, 2017

High above Earth, two giant rings of energetic particles trapped by the planet's magnetic field create a dynamic and harsh environment that holds many mysteries—and can affect spacecraft traveling around Earth. NASA's Van ...

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.