TY - JOUR
T1 - Gelator Length Precisely Tunes Supramolecular Hydrogel Stiffness and Neuronal Phenotype in 3D Culture
AU - Godbe, Jacqueline M.
AU - Freeman, Ronit
AU - Burbulla, Lena F.
AU - Lewis, Jacob
AU - Krainc, Dimitri
AU - Stupp, Samuel I.
N1 - Funding Information:
Funding for this work was provided by the Paul Ruby Foundation for Parkinson’s Disease, a Catalyst Award from the Center for Regenerative Nanomedicine at the Simpson Querrey Institute at Northwestern University, and NIH grants R01 NS076054 and R37 NS096241 to D.K. Peptide synthesis and purification were 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). This work made use of the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. 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. Mechanical analysis was performed in the Analytical BioNanoTechnology Equipment Core 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). The authors acknowledge helpful discussions with Chris Serrano and Dr. Mark Karver of the authors’ laboratory and the Simpson Querrey Institute, respectively.
PY - 2020/2/10
Y1 - 2020/2/10
N2 - The brain is one of the softest tissues in the body with storage moduli (G′) that range from hundreds to thousands of pascals (Pa) depending on the anatomic region. Furthermore, pathological processes such as injury, aging, and disease can cause subtle changes in the mechanical properties throughout the central nervous system. However, these changes in mechanical properties lie within an extremely narrow range of moduli, and there is great interest in understanding their effect on neuron biology. We report here the design of supramolecular hydrogels based on anionic peptide amphiphile nanofibers using oligo-l-lysines of different molecular lengths to precisely tune gel stiffness over the range of interest and found that G′ increases by 10.5 Pa for each additional lysine monomer in the oligo-l-lysine chain. We found that small changes in storage modulus on the order of 70 Pa significantly affect survival, neurite growth, and tyrosine hydroxylase-positive population in dopaminergic neurons derived from induced pluripotent stem cells. The work reported here offers a strategy to tune mechanical stiffness of hydrogels for use in three-dimensional neuronal cell cultures and transplantation matrices for neural regeneration.
AB - The brain is one of the softest tissues in the body with storage moduli (G′) that range from hundreds to thousands of pascals (Pa) depending on the anatomic region. Furthermore, pathological processes such as injury, aging, and disease can cause subtle changes in the mechanical properties throughout the central nervous system. However, these changes in mechanical properties lie within an extremely narrow range of moduli, and there is great interest in understanding their effect on neuron biology. We report here the design of supramolecular hydrogels based on anionic peptide amphiphile nanofibers using oligo-l-lysines of different molecular lengths to precisely tune gel stiffness over the range of interest and found that G′ increases by 10.5 Pa for each additional lysine monomer in the oligo-l-lysine chain. We found that small changes in storage modulus on the order of 70 Pa significantly affect survival, neurite growth, and tyrosine hydroxylase-positive population in dopaminergic neurons derived from induced pluripotent stem cells. The work reported here offers a strategy to tune mechanical stiffness of hydrogels for use in three-dimensional neuronal cell cultures and transplantation matrices for neural regeneration.
KW - hydrogels
KW - mechanical properties
KW - neurons
KW - peptide amphiphiles
KW - supramolecular
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U2 - 10.1021/acsbiomaterials.9b01585
DO - 10.1021/acsbiomaterials.9b01585
M3 - Article
AN - SCOPUS:85078536071
VL - 6
SP - 1196
EP - 1207
JO - ACS Biomaterials Science and Engineering
JF - ACS Biomaterials Science and Engineering
SN - 2373-9878
IS - 2
ER -