TY - JOUR
T1 - Mimicking the Bioactivity of Fibroblast Growth Factor-2 Using Supramolecular Nanoribbons
AU - Rubert Pérez, Charles M.
AU - Álvarez, Zaida
AU - Chen, Feng
AU - Aytun, Taner
AU - Stupp, Samuel I.
N1 - Funding Information:
The studies reported here were supported by the National Institute of Health PPG (5P01HL108795-05) and by the National Institute of Health Bioengineering Research Partnership (BRP) (5R01EB003806-09) research grants. C.M.R.P. gratefully acknowledges support from the National Institute of Health NIBIB Supplement Award (3R01EB003806-09S1). Additional support for T.A. to perform atomic force microscopy experiments was provided by the U.S. Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, under award no. DE-FG02-00ER45810. Z.A. received postdoctoral support from the Beatriu de Pinoś Fellowship 2014 BP-A 00007 (Ageǹcia de Gestió d’Ajust Universitaris i de Recerca, AGAUR). PA synthesis was performed in the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University. The U.S. Army Research Office, the U.S. Army Medical Research and Materiel Command, and Northwestern University provided funding to develop this facility, and ongoing support is being received from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205). Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. CD experiments were performed using the Keck Biophysics Facility at Northwestern University. TEM and AFM experiments were performed at the EPIC facility of the NUANCE Center at Northwestern University, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF NNCI-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. We thank Mark McClendon for SEM experiments and Mark Seniw for schematic illustrations and helpful discussions.
PY - 2017/9/11
Y1 - 2017/9/11
N2 - 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.
AB - 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.
KW - fibroblast growth factor-2 mimetic peptide
KW - nanoribbons
KW - peptide amphiphiles
KW - supramolecular biomaterials
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U2 - 10.1021/acsbiomaterials.7b00347
DO - 10.1021/acsbiomaterials.7b00347
M3 - Article
AN - SCOPUS:85029452878
VL - 3
SP - 2166
EP - 2175
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
SN - 2373-9878
IS - 9
ER -