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Cytokines and growth factors cross-link heparan sulfate
- Source :
- Open Biology, Vol 5, Iss 8 (2015), OPEN BIOLOGY, Open Biology, Open Biology, Royal Society, 2015, 5, pp.150046. ⟨10.1098/rsob.150046⟩, Open Biology, 2015, 5, pp.150046. ⟨10.1098/rsob.150046⟩
- Publication Year :
- 2015
- Publisher :
- The Royal Society, 2015.
-
Abstract
- The glycosaminoglycan heparan sulfate (HS), present at the surface of most cells and ubiquitous in extracellular matrix, binds many soluble extracellular signalling molecules 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 supramolecular 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 biophysical techniques quartz crystal microbalance (QCM-D) and fluorescence recovery after photobleaching (FRAP). We were able to control and characterize the supramolecular presentation of HS chains—their local density, orientation, conformation and lateral mobility—and their interaction with proteins. The chemokine CXCL12 α (or SDF-1 α ) rigidified the HS film, and this effect was due to protein-mediated cross-linking of HS chains. Complementary measurements with CXCL12 α mutants and the CXCL12 γ isoform provided insight into the molecular mechanism underlying cross-linking. 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-chemical 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.
- Subjects :
- Models, Molecular
medicine.medical_treatment
extracellular matrix
Immunology
Molecular Conformation
Fluorescence recovery after photobleaching (FRAP)
Plasma protein binding
Biology
Matrix (biology)
Fibroblast growth factor
General Biochemistry, Genetics and Molecular Biology
chemistry.chemical_compound
medicine
Extracellular
cytokine
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Binding site
lcsh:QH301-705.5
Research Articles
Glycosaminoglycans
Quartz crystal microbalance (QCM-D)
Research
General Neuroscience
Growth factor
chemokine
Fluorescence recovery after photobleaching
growth factor
Heparan sulfate
Chemokine CXCL12
Biochemistry
chemistry
lcsh:Biology (General)
glycosaminoglcyan
Biophysics
Intercellular Signaling Peptides and Proteins
Cytokines
Heparitin Sulfate
heparan sulfate
Growth factors
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 20462441
- Database :
- OpenAIRE
- Journal :
- Open Biology, Vol 5, Iss 8 (2015), OPEN BIOLOGY, Open Biology, Open Biology, Royal Society, 2015, 5, pp.150046. ⟨10.1098/rsob.150046⟩, Open Biology, 2015, 5, pp.150046. ⟨10.1098/rsob.150046⟩
- Accession number :
- edsair.doi.dedup.....d2c010c8a95f9abd302c13b818d1a489
- Full Text :
- https://doi.org/10.1098/rsob.150046⟩