Nanomechanics on FGF-2 and heparin reveal slip bond characteristics with pH dependency
Sevim, Semih (Bogazici University. Department of Electrical and Electronics Engineering)
Ozer, Sevil (Bogazici University. Department of Electrical and Electronics Engineering)
Jones, Gabriel (Universität Würzburg. Institute of Pharmacy and Food Chemistry)
Wurzel, Joel (Universität Würzburg. Institute of Pharmacy and Food Chemistry)
Feng, Luying (Bogazici University. Department of Electrical and Electronics Engineering)
Fakhraee, Arielle (Aeon Scientific AG)
Shamsudhin, Naveen (ETH Zürich. Institute of Robotics and Intelligent Systems)
Ergeneman, Olga (ETH Zürich. Institute of Robotics and Intelligent Systems)
Pellicer Vilà, Eva Maria (Universitat Autònoma de Barcelona. Departament de Física)
Sort Viñas, Jordi (Universitat Autònoma de Barcelona. Departament de Física)
Pané i Vidal, Salvador (ETH Zürich. Institute of Robotics and Intelligent Systems)
Nelson, Bradley J. (ETH Zürich. Institute of Robotics and Intelligent Systems)
Torun, Hamdi (Bogazici University. Department of Electrical and Electronics Engineering)
Lühmann, Tessa (Universität Würzburg. Institute of Pharmacy and Food Chemistry)

Data:	2017
Resum:	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.
Ajuts:	European Commission 296679
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió sotmesa a revisió
Matèria:	Atomic force spectroscopy ; Extracellular matrix ; Hypoxia ; Isothermal titration calorimetry ; Magnetic actuation
Publicat a:	ACS biomaterials science & engineering, Vol. 3, issue 6 (2017) , p. 1000-1007, ISSN 2373-9878

DOI: 10.1021/acsbiomaterials.6b00723

Preprint 30 p, 759.1 KB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències > Grup de nanoenginyeria de materials, nanomagnetisme i nanomecànica (Gnm3)
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