Scientists get closest look yet at human tissue

Scientists from the European Molecular Biology Laboratory (EMBL) have published the first ever three-dimensional (3D) image of human skin at molecular resolution, the image reveals the
molecular Velcro-like structure that interlinks the skin cells.

Examining proteins in their natural environment, as well as the interactions inside cells, has eluded scientists until now. Previous methods used low resolution images or involved treating the
tissue with chemicals, or coating it in metal. This interferes with the natural state of the sample.

Using an advanced microscopy technique known as cryo-electron tomography, Achilleas Frangakis and team have been able to freeze a cell or tissue in its natural state, and then examine it with
an electron microscope. Images are taken of the untreated sample from different directions and compiled to create an accurate 3D image by a computer.

‘This is a real breakthrough in two respects,’ says Dr Frangakis. ‘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.’

The team has already used its technique to observe proteins that are key to the functioning of tissues and organs such as the skin and the heart, and that also play an important role in cell
proliferation. These proteins, called cadherins, are found within cell membranes, and interact with one another to bring cells close together and interlink them tightly.

Ashraf Al-Amoudi was a member of Dr Frangakis’ team. ‘We could see the interaction between the two cadherins directly, and this revealed where the strength of human skin comes from,’ he said.
‘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 research was published in the journal Nature on 6 December.