The closest look ever at native human tissue

Dec 05, 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: GMO mosquito plan sparks outcry in Florida

add to favorites email to friend print save as pdf

Related Stories

DNA nanoswitches reveal how life's molecules connect

23 hours ago

A complex interplay of molecular components governs almost all aspects of biological sciences - healthy organism development, disease progression, and drug efficacy are all dependent on the way life's molecules ...

In a role reversal, RNAs proofread themselves

Jan 29, 2015

Building a protein is a lot like a game of telephone: information is passed along from one messenger to another, creating the potential for errors every step of the way. There are separate, specialized enzymatic ...

Recommended for you

GMO mosquito plan sparks outcry in Florida

6 hours ago

A British company's plan to unleash hordes of genetically modified mosquitoes in Florida to reduce the threat of dengue fever and other diseases has sparked an outcry from fearful residents.

Population genomics unveil seahorse domain

Jan 30, 2015

In a finding vital to effective species management, a team including City College of New York biologists has determined that the lined seahorse (Hippocampus erectus) is more a permanent resident of the we ...

User comments : 0

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.