Unbinding Kinetics of Syndecans by Single-Molecule Force Spectroscopy.

Syndecans are transmembrane proteoglycans that, together with integrins, control cell interactions with extracellular matrix components. Despite structural similarities between all members of the syndecan family, their specific attachment to extracellular matrix proteins is defined by heparan and chondroitin chains. We postulate various unbinding kinetics for each type of single syndecan complex. Force spectroscopy data, recorded by atomic force microscope, were analyzed using two theoretical approaches describing force-induced unbinding, authored by Bell-Evans and Dudko-Hummer-Szabo. Our results reveal distinct unbinding pathways dependent on the syndecan family member. Syndecan-1 unbinds by passing over two energy barriers, inner and outer. Syndecan-4 unbinds by crossing over only one energy barrier. It has already been reported that both syndecans bear heparan chains that are structurally indistinguishable. Our finding reveals that unbinding of single syndecan complexes is family-member-dependent. Distinct unbinding pathways can be attributed to structural differences of heparan and chondroitin chains.