Conferencias, RedBIOT

Por defecto: 
Artificial Extracellular Matrix Scaffolds of Mobile Molecules Enhance Maturation of Human Stem Cell-Derived Neurons
Zaida Alvarez Pinto

Construir: Edificio E
Sala: Audiovisual
Fecha: 2022-10-26 09:20 AM – 10:20 AM
Última modificación: 2022-10-19


Human induced pluripotent stem cell (iPSC) 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 derived from the architecture, chemical composition and molecular dynamics of the native extracellular matrix (ECM). We report on the use of three artificial ECMs based on supramolecular nanofibers containing peptide amphiphile molecules. All nanofibers display on their surface the laminin-derived IKVAV signal 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 iPSC-derived motor and cortical neurons. Proteomic, biochemical and functional assays reveal that scaffolds with highly mobile molecules lead to enhanced  b1-integrin pathway activation, reduced aggregation, increased arborization, and mature electrophysiological activity of neurons. Our work highlights the importance of designing bioactive ECMs to study the development, function and dysfunction of human neurons in vitro.

Palabras clave

hydrogel, dynamics, peptide amphiphiles, neurons, iPSCs, motion, laminin