Cells of the body are constantly communicating with their surroundings. This integration of cells with their local environment is mediated by proteins on the surface of cells called integrin adhesion receptors. But how these proteins precisely control normal cellular functions is not well understood. In fact, it turns out to be extremely complex.

In new work, this complexity of cellular signalling is analysed. Distilling down the deluge of data allowed us to discover a key collection of components that congregate at sites of cell adhesion. These proteins play important roles in allowing cells to sense their surroundings, move and survive. When these processes go wrong, diseases like cancer can develop.

Our work is also featured on the cover of this month’s issue of Nature Cell Biology, with an image by Ed Horton showing all the proteins we analysed. See if you can spot your favourite adhesion protein!

Nature Cell Biology cover, 2015, vol. 17 (no. 12) // Image by Ed Horton

Nature Cell Biology cover, 2015, vol. 17 (no. 12)

Proteins that control the adhesion and sensing of the body’s cells collect at the cells’ outer membranes in clusters called adhesion complexes. Over the past several years, advances in biochemical methods to isolate and analyse these collections of proteins have allowed us and other scientists to catalogue the composition of these complexes.

These catalogues (sometimes called ‘adhesomes‘) are large, with many hundreds of proteins detected in most cells. But what can all these proteins be doing, and are they all important?

We set out to try to understand these questions better by using a systems-level approach. This meant that, rather than examining each protein in an adhesion complex on an individual basis, we looked at all the proteins detected in these complexes and how they may interact with each other: we studied the cell adhesion ‘system’.

By taking this ‘global’ approach, we were able to appreciate the complexity of the numerous proteins involved in cell adhesion. But we were also able to use computers to start untangling this complexity to reveal the proteins that were found at cell adhesions most often. We propose that these proteins, of which there are 60, form a core cell adhesion machinery – a ‘consensus adhesome’.

We could understand better how these crucial protein clusters form and grow.

Although the precise composition of the consensus adhesome may change over time as new adhesion sites are characterised and more data become available, it has already proved to be a useful tool for the interpretation of the complexity of cell adhesion sites.

For example, we isolated adhesion complexes during their assembly and disassembly and used the consensus adhesome to assess the recruitment of the core cell adhesion machinery to the cell membrane. This allowed us not just to focus on the well studied adhesion proteins but also to examine the dynamics of underappreciated components of cell adhesion. From these analyses, we could understand better how these crucial protein clusters form and grow.

This fundamental understanding of how cells function will help us to work out which sets of proteins are most important to prevent diseases like cancer, in which the body’s cells adhere and move incorrectly, from progressing.

These datasets are vast and will continue to grow, allowing us and others to mine and modify the data resource to work towards a more accurate understanding of, and for brand new insights into, the significance of the stickiness of our cells.

The work has also been press released today here and here.

This work was supported by the Wellcome Trust, the BBSRC and the University of Manchester.

Horton et al. Definition of a consensus integrin adhesome and its dynamics during adhesion complex assembly and disassembly. Nat. Cell Biol. 17, 1577–1587 (2015)