Single-molecule force spectroscopy reveals structural differences of heparan sulfate chains during binding to vitronectin

TL;DR

This study uses single-molecule force spectroscopy to uncover structural differences in heparan sulfate chains of syndecans during binding to vitronectin, revealing potential implications for cancer progression and therapeutic targeting.

Contribution

It provides novel insights into the unbinding properties and structural variations of syndecan heparan sulfate chains during interaction with vitronectin at the single-molecule level.

Findings

Syndecans are calcium-dependent molecules with distinct unbinding properties.

Structural alterations in heparan sulfate chains influence binding to ECM proteins.

These differences may affect cancer cell invasion and signaling pathways.

Abstract

The syndecans represent an ongoing research field focused on their regulatory roles in normal and pathological conditions. Syndecan's role in cancer progression becomes well-documented, implicating their importance in diagnosis and even proposing various cancer potential treatments. Thus, the characterization of the unbinding properties at the single molecules level will appeal to their use as targets for therapeutics. In our study, syndecan-1 and syndecan-4 were measured during the interaction with the vitronectin HEP II binding site. Our findings show that syndecans are calcium ion-dependent molecules that reveal distinct, unbinding properties indicating the alterations in heparin sulfate chain structure, possibly in the chain sequence or sulfation pattern. In that way, we suppose that HS chain affinity to ECM proteins may govern cancer invasion by altering syndecan ability to interact with cancer-related receptors present in the tumor microenvironment, thereby promoting the activation of various signaling cascades regulating tumor cell behavior.