Martin Humphries, University of Manchester, UK, tells Soft Matter about his hot paper in the Proteins and Cells at Functional Interfaces theme issue

1. Can you briefly describe what you achieved in this article?
We have used this article to examine the efficiency with which recombinant ligands, traditionally used to dissect the contributions of different transmembrane receptors to cell adhesion, can be immobilised on surfaces and support adhesion formation.  Through this analysis we have demonstrated the absolute interdependence of integrins and syndecan-4 for the adhesive response to fibronectin, and shown that neither receptor can compensate for the other by increasing the density of a single ligand.

2. Could you explain the significance of your article to the non-specialist?
Until recently, the cell adhesion field has largely focused on the integrin family of matrix receptors, to the extent that we have assumed that all signals initiated in response to a cell's matrix environment can be attributed to integrin engagement.  However, the ability of cells to modulate adhesive capabilities, according to external stimuli and developmental stage, is critical to the survival of an organism.  Consequently, the need to resolve the extent of cooperation between receptors is a subject of growing urgency, where the dose effects of different ligands must be tempered against the role of different receptors working in synergy.

3. What has motivated you to conduct this work?
Our work is progressing towards the study of cooperative signalling by adhesion receptors and, like any new project, there was a need to examine the experimental conditions to ensure that the biological conclusions drawn by ourselves, and others, are not an artefact based on chemical or physical problems in the assay.  In addition to avoiding such pitfalls ourselves, the publication of the study enables the field as a whole to advance in this area without the continued debate over validity.

4. Where do you see this work developing in the future?
We are presently investigating the role of receptor synergy, between integrin and syndecan-4, in the regulation of downstream signals including PKCalpha and small Rho-family GTPases.  Specifically we are investigating the effect of these signals on cell migration with a view to understanding the mechanism of wound closure.

5. Are there any particular challenges facing future research in this area?
We have already outlined the importance of understanding receptor synergy for the advancement of adhesion biology, but a more specific challenge underlies the interest in syndecan-4.  Syndecan-4 knockout mice exhibit a very specific defect, namely a delay in the healing of dermal wounds.  By understanding the mechanisms by which organisms close dermal wounds, we become better positioned for the development of pharmacological agents that will assist the healing process in vivo.