Mimicking the Bioactivity of Fibroblast Growth Factor-2 Using Supramolecular Nanoribbons

Abstract

Fibroblast growth factor (FGF-2) is a multifunctional growth factor that has pleiotropic effects in different tissues and organs. In particular, FGF-2 has a special role in angiogenesis, an important process in development, wound healing, cell survival, and differentiation. Therefore, incorporating biological agents like FGF-2 within therapeutic biomaterials is a potential strategy to create angiogenic bioactivity for the repair of damaged tissue caused by trauma or complications that arise from age and/or disease. However, the use of growth factors as therapeutic agents can be costly and does not always bring about efficient tissue repair due to rapid clearance from the targeted site. An alternative would be a stable supramolecular nanostructure with the capacity to activate the FGF-2 receptor that can also assemble into a scaffold deliverable to tissue. We report here on peptide amphiphiles that incorporate a peptide known to activate the FGF-2 receptor and peptide domains that drive its self-assembly into supramolecular nanoribbons. These FGF2-PA nanoribbons displayed the ability to increase the proliferation and migration of the human umbilical vein endothelial cells (HUVECs) in vitro to the same extent as the native FGF-2 protein at certain concentrations. We confirmed that this activity was specific to the FGFR1 signaling pathway by tracking the phosphorylation of downstream signaling effectors such ERK1/2 and pH3. These results indicated the specificity of FGF2-PA nanoribbons in activating the FGF-2 signaling pathway and its potential application as a supramolecular scaffold that can be used in vivo as an alternative to the encapsulation and delivery of the native FGF-2 protein.

Minimalistic supramolecular proteoglycan mimics by co-assembly of aromatic peptide and carbohydrate amphiphiles

“…Basic fibroblast growth factor (FGF-2) is a glycoprotein that has a pleiotropic effect in different tissues and organs: it is crucial for processes such as angiogenesis, development, wound healing, cell survival and differentiation, among others 35,36. It is also known for its thermal instability: it loses most of its activity after 24 h of incubation at 37 °C (Fig.…”

Supramolecular scaffolds enabling the controlled assembly of functional molecular units

“…Stupp and coworkers reported that a series of peptide amphiphile (PA) building blocks such as 64–69 self-assemble into 1D fibres, which have many biological applications. 21 , 87 – 95 Typically, PAs have a long alkyl chain (C 13 –C 16 ) at the N-terminus of the peptide, a β-sheet-forming part, a charge-containing part, and a functional unit domain at the C-terminus ( Fig. 11 ).…”

Supramolecular Nanostructure Activates TrkB Receptor Signaling of Neuronal Cells by Mimicking Brain-Derived Neurotrophic Factor

“… 30 PAs have been shown to be highly bioactive and mimic natural extracellular matrices 21 ,. 31 – 33 We previously developed PAs displaying diverse bioactive epitopes such as IKVAV, FGF-2, and VEGF with the ability to activate β−1 integrin, 34 , 35 FGFR-1, 36 and VEGFR-1 21 receptors, respectively. We report here on the incorporation of the RKKA d P BDNF mimetic peptide on a PA capable of assembling in aqueous media into one-dimensional supramolecular nanostructures.…”