### Cytokines and growth factors cross-link heparan sulfate.

The glycosaminoglycan heparan sulfate (HS), present at the surface of most cells and ubiquitous in extracellular matrix, binds many sol. extracellular signalling mols. such as chemokines and growth factors, and regulates their transport and effector functions. It is, however, unknown whether upon binding HS these proteins can affect the long-range structure of HS. To test this idea, we interrogated a supramol. model system, in which HS chains grafted to streptavidin-functionalized oligoethylene glycol monolayers or supported lipid bilayers mimic the HS-rich pericellular or extracellular matrix, with the biophys. techniques quartz crystal microbalance (QCM-D) and fluorescence recovery after photobleaching (FRAP). We were able to control and characterize the supramol. presentation of HS chains-their local d., orientation, conformation and lateral mobility-and their interaction with proteins. The chemokine CXCL12$\alpha$ (or SDF-1$\alpha$) rigidified the HS film, and this effect was due to protein-mediated crosslinking of HS chains. Complementary measurements with CXCL12$\alpha$ mutants and the CXCL12$\gamma$ isoform provided insight into the mol. mechanism underlying crosslinking. Fibroblast growth factor 2 (FGF-2), which has three HS binding sites, was also found to cross-link HS, but FGF-9, which has just one binding site, did not. Based on these data, we propose that the ability to cross-link HS is a generic feature of many cytokines and growth factors, which depends on the architecture of their HS binding sites. The ability to change matrix organization and physico-chem. properties (e.g. permeability and rigidification) implies that the functions of cytokines and growth factors may not simply be confined to the activation of cognate cellular receptors. [on SciFinder(R)]

### Références

Titre
Cytokines and growth factors cross-link heparan sulfate.
Type de publication
Article de revue
Année de publication
2015
Revue
Open Biol.
Volume
5
Pagination
150046/1–150046/15
ISSN
2046-2441
Soumis le 12 avril 2018