Single-Molecule Unbinding Forces between the Polysaccharide Hyaluronan and Its Binding Proteins

Fouzia Bano, Markku I. Tammi, David W. Kang, Edward N. Harris, Ralf P. Richter

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The extracellular polysaccharide hyaluronan (HA) is ubiquitous in all vertebrate tissues, where its various functions are encoded in the supramolecular complexes and matrices that it forms with HA-binding proteins (hyaladherins). In tissues, these supramolecular architectures are frequently subjected to mechanical stress, yet how this affects the intermolecular bonding is largely unknown. Here, we used a recently developed single-molecule force spectroscopy platform to analyze and compare the mechanical strength of bonds between HA and a panel of hyaladherins from the Link module superfamily, namely the complex of the proteoglycan aggrecan and cartilage link protein, the proteoglycan versican, the inflammation-associated protein TSG-6, the HA receptor for endocytosis (stabilin-2/HARE), and the HA receptor CD44. We find that the resistance to tensile stress for these hyaladherins correlates with the size of the HA-binding domain. The lowest mean rupture forces are observed for members of the type A subgroup (i.e., with the shortest HA-binding domains; TSG-6 and HARE). In contrast, the mechanical stability of the bond formed by aggrecan in complex with cartilage link protein (two members of the type C subgroup, i.e., with the longest HA-binding domains) and HA is equal or even superior to the high affinity streptavidin⋅biotin bond. Implications for the molecular mechanism of unbinding of HA⋅hyaladherin bonds under force are discussed, which underpin the mechanical properties of HA⋅hyaladherin complexes and HA-rich extracellular matrices.

Original languageEnglish (US)
Pages (from-to)2910-2922
Number of pages13
JournalBiophysical journal
Volume114
Issue number12
DOIs
StatePublished - Jun 19 2018

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CD44 Antigens
Hyaluronic Acid
Polysaccharides
Aggrecans
Proteoglycans
Versicans
Mechanical Stress
Endocytosis
Extracellular Matrix
Vertebrates
Rupture
Inflammation

ASJC Scopus subject areas

  • Biophysics

Cite this

Single-Molecule Unbinding Forces between the Polysaccharide Hyaluronan and Its Binding Proteins. / Bano, Fouzia; Tammi, Markku I.; Kang, David W.; Harris, Edward N.; Richter, Ralf P.

In: Biophysical journal, Vol. 114, No. 12, 19.06.2018, p. 2910-2922.

Research output: Contribution to journalArticle

Bano, Fouzia ; Tammi, Markku I. ; Kang, David W. ; Harris, Edward N. ; Richter, Ralf P. / Single-Molecule Unbinding Forces between the Polysaccharide Hyaluronan and Its Binding Proteins. In: Biophysical journal. 2018 ; Vol. 114, No. 12. pp. 2910-2922.
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