Nanomechanics on FGF-2 and Heparin Reveal Slip Bond Characteristics with pH Dependency

Semih Sevim, Sevil Ozer, Gabriel Jones, Joel Wurzel, Luying Feng, Arielle Fakhraee, Naveen Shamsudhin, Olgaç Ergeneman, Eva Pellicer, Jordi Sort, Salvador Pané, Bradley J. Nelson, Hamdi Torun, Tessa Lühmann

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

© 2017 American Chemical Society. Fibroblast growth factor 2 (FGF-2), an important paracrine growth factor, binds electrostatically with low micromolar affinity to heparan sulfates present on extracellular matrix proteins. A single molecular analysis served as a basis to decipher the nanomechanical mechanism of the interaction between FGF-2 and the heparan sulfate surrogate, heparin, with a modular atomic force microscope (AFM) design combining magnetic actuators with force measurements at the low force regime (1 × 101 to 1 × 104 pN/s). Unbinding events between FGF-2-heparin complexes were specific and short-lived. Binding between FGF-2 and heparin had strong slip bond characteristics as demonstrated by a decrease of lifetime with tensile force on the complex. Unbinding forces between FGF-2 and heparin were further detailed at different pH as relevant for (patho-) physiological conditions. An acidic pH environment (5.5) modulated FGF-2-heparin binding as demonstrated by enhanced rupture forces needed to release FGF-2 from the heparin-FGF-2 complex as compared to physiological conditions. This study provides a mechanistic and hypothesis driven model on how molecular forces may impact FGF-2 release and storage during tissue remodeling and repair.
Original languageEnglish
Pages (from-to)1000-1007
JournalACS Biomaterials Science and Engineering
Volume3
Issue number6
DOIs
Publication statusPublished - 12 Jun 2017

Keywords

  • atomic force spectroscopy
  • extracellular matrix
  • hypoxia
  • isothermal titration calorimetry
  • magnetic actuation

Fingerprint Dive into the research topics of 'Nanomechanics on FGF-2 and Heparin Reveal Slip Bond Characteristics with pH Dependency'. Together they form a unique fingerprint.

Cite this