Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons.
Cell Stem Cell
; 30(2): 219-238.e14, 2023 02 02.
Article
em En
| MEDLINE
| ID: mdl-36638801
ABSTRACT
Human induced pluripotent stem cell (hiPSC) technologies offer a unique resource for modeling neurological diseases. However, iPSC models are fraught with technical limitations including abnormal aggregation and inefficient maturation of differentiated neurons. These problems are in part due to the absence of synergistic cues of the native extracellular matrix (ECM). We report on the use of three artificial ECMs based on peptide amphiphile (PA) supramolecular nanofibers. All nanofibers display the laminin-derived IKVAV signal on their surface but differ in the nature of their non-bioactive domains. We find that nanofibers with greater intensity of internal supramolecular motion have enhanced bioactivity toward hiPSC-derived motor and cortical neurons. Proteomic, biochemical, and functional assays reveal that highly mobile PA scaffolds caused enhanced ß1-integrin pathway activation, reduced aggregation, increased arborization, and matured electrophysiological activity of neurons. Our work highlights the importance of designing biomimetic ECMs to study the development, function, and dysfunction of human neurons.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Pluripotentes Induzidas
/
Nanofibras
Limite:
Humans
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Espanha