Nanomechanics on FGF-2 and heparin reveal slip bond characteristics with pH dependency
| Autor: | Hamdi Torun, Tessa Lühmann, Naveen Shamsudhin, Bradley J. Nelson, Arielle Fakhraee, Joel Wurzel, Sevil Ozer, Olgaç Ergeneman, Jordi Sort, Salvador Pané, Semih Sevim, Eva Pellicer, Luying Feng, Gabriel Jones |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Biomedical Engineering Slip (materials science) Fibroblast growth factor Biomaterials Extracellular matrix 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Hypoxia Chemistry Growth factor Isothermal titration calorimetry Heparan sulfate Heparin Magnetic actuation C700 Crystallography 030104 developmental biology Atomic force spectroscopy 030217 neurology & neurosurgery Nanomechanics medicine.drug |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| ISSN: | 2373-9878 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|