Modifications of hyaluronan influence the interaction with human bone morphogenetic protein-4 (hBMP-4)

Biomacromolecules. 2009 Dec 14;10(12):3290-7. doi: 10.1021/bm9008827.


In this study, we have demonstrated that the modification of hyaluronan (hyaluronic acid; Hya) with sulfate groups led to different binding affinities for recombinant human bone morphogenetic protein-4 (rhBMP-4). The high-sulfated sHya2.8 (average degree of sulfation (D.S.) 2.8) exhibited the tightest interaction with rhBMP-4, followed by the low-sulfated sHya1.0, as determined with surface plasmon resonance (SPR), ELISA, and competition ELISA. Unmodified Hya, chondroitin-sulfate (CS), and heparan sulfate (HS) showed significantly less binding affinity. SPR data could be fitted to an A + B = AB Langmuir model and binding constants were evaluated ranging from 13 pM to 5.45 microM. The interaction characteristics of the differentially sulfated Hyas are promising for the incorporation of these modified polysaccharides in bioengineered coatings of biomaterials for medical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques
  • Bone Morphogenetic Protein 4 / chemistry*
  • Bone Morphogenetic Protein 4 / genetics
  • Chondroitin Sulfates / chemistry
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Hyaluronic Acid / chemistry*
  • Immobilized Proteins / chemistry*
  • Immobilized Proteins / genetics
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Sulfuric Acid Esters / chemistry*
  • Surface Plasmon Resonance


  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • Immobilized Proteins
  • Recombinant Proteins
  • Sulfuric Acid Esters
  • Hyaluronic Acid
  • Chondroitin Sulfates