Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons

Zaida Álvarez, J. Alberto Ortega, Kohei Sato, Ivan R. Sasselli, Alexandra N. Kolberg-Edelbrock, Ruomeng Qiu, Kelly A. Marshall, Thao Phuong Nguyen, Cara S. Smith, Katharina A. Quinlan, Vasileios Papakis, Zois Syrgiannis, Nicholas A. Sather, Chiara Musumeci, Elisabeth Engel, Samuel I. Stupp*, Evangelos Kiskinis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 β1-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.

Original languageEnglish (US)
Pages (from-to)219-238.e14
JournalCell stem cell
Volume30
Issue number2
DOIs
StatePublished - Feb 2 2023

Keywords

  • IKVAV
  • dynamics
  • extracellular matrix
  • iPSC-derived neurons
  • laminin
  • neuronal maturation
  • peptide amphiphiles
  • supramolecular motion
  • supramolecular nanofibers

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Cell Biology

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