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

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Sevim S., Ozer S., Jones G., Wurzel J., Feng L., Fakhraee A., ...Daha Fazla

ACS Biomaterials Science and Engineering, cilt.3, sa.6, ss.1000-1007, 2017 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 3 Sayı: 6
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1021/acsbiomaterials.6b00723
  • Dergi Adı: ACS Biomaterials Science and Engineering
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1000-1007
  • Anahtar Kelimeler: atomic force spectroscopy, extracellular matrix, hypoxia, isothermal titration calorimetry, magnetic actuation
  • İstanbul Yeni Yüzyıl Üniversitesi Adresli: Evet

Özet

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.