Probing the recognition specificity of αVβ1 integrin and syndecan-4 using force spectroscopy

Micron. 2020 Oct:137:102888. doi: 10.1016/j.micron.2020.102888. Epub 2020 Jun 1.

Abstract

The knowledge on how cells interact with microenvironment is particularly important in understanding the interaction of cancer cells with surrounding stroma, which affects cell migration, adhesion, and metastasis. The main cell surface receptors responsible for the interaction with extracellular matrix (ECM) are integrins, however, they are not the only ones. Integrins are accompanied to other molecules such as syndecans. The role of the latter has not yet been fully established. In our study, we would like to answer the question of whether integrins and syndecans, possessing similar functions, share also similar unbinding properties. By using single molecule force spectroscopy (SMFS), we conducted measurements of the unbinding properties of αVβ1 and syndecan-4 in the interaction with vitronectin (VN), which, as each ECM protein, possesses two binding sites specific to integrins and syndecans. The unbinding force and the kinetic off rate constant derived from SMFS describe the stability of single molecular complex. Obtained data show one barrier transition for each complex. The proposed model shows that the unbinding of αVβ1 from VN proceeds before the unbinding of SDC-4. However, despite different unbinding kinetics, the access to both receptors is needed for cell growth and proliferation.

Keywords: Integrins; Single molecule force spectroscopy; Specific recognition; Syndecans; Vitronectin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Line, Tumor
  • Extracellular Matrix
  • Humans
  • Integrin alpha5beta1 / chemistry*
  • Integrin alpha5beta1 / genetics
  • Integrin alpha5beta1 / metabolism*
  • Single Molecule Imaging / methods*
  • Syndecan-4 / chemistry*
  • Syndecan-4 / genetics
  • Syndecan-4 / metabolism*
  • Urinary Bladder Neoplasms
  • Vitronectin / metabolism

Substances

  • Integrin alpha5beta1
  • SDC4 protein, human
  • Syndecan-4
  • Vitronectin