Effects of amyloid-β-mimicking peptide hydrogel matrix on neuronal progenitor cell phenotype.

Autor: Mathes TG; Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, CA, USA., Monirizad M; Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, CA, USA., Ermis M; Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, CA, USA; BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering Middle East Technical University, Ankara 06800, Turkey., de Barros NR; Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, CA, USA., Rodriguez M; Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, CA, USA., Kraatz HB; Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON M5S 2E4, Canada; Department of Physical and Environmental Science, University of Toronto Scarborough, Toronto, ON M1C 1A4, Canada., Jucaud V; Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, CA, USA., Khademhosseini A; Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, CA, USA. Electronic address: khademh@terasaki.org., Falcone N; Terasaki Institute for Biomedical Innovation (TIBI), 1018 Westwood Blvd, Los Angeles, CA, USA. Electronic address: nfalcone@terasaki.org.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2024 Jul 15; Vol. 183, pp. 89-100. Date of Electronic Publication: 2024 May 25.
DOI: 10.1016/j.actbio.2024.05.020
Abstrakt: Self-assembling peptide-based hydrogels have become a highly attractive scaffold for three-dimensional (3D) in vitro disease modeling as they provide a way to create tunable matrices that can resemble the extracellular matrix (ECM) of various microenvironments. Alzheimer's disease (AD) is an exceptionally complex neurodegenerative condition; however, our understanding has advanced due to the transition from two-dimensional (2D) to 3D in vitro modeling. Nonetheless, there is a current gap in knowledge regarding the role of amyloid structures, and previously developed models found long-term difficulty in creating an appropriate model involving the ECM and amyloid aggregates. In this report, we propose a multi-component self-assembling peptide-based hydrogel scaffold to mimic the amyloid-beta (β) containing microenvironment. Characterization of the amyloid-β-mimicking hydrogel (Col-HAMA-FF) reveals the formation of β-sheet structures as a result of the self-assembling properties of phenylalanine (Phe, F) through π-π stacking of the residues, thus mimicking the amyloid-β protein nanostructures. We investigated the effect of the amyloid-β-mimicking microenvironment on healthy neuronal progenitor cells (NPCs) compared to a natural-mimicking matrix (Col-HAMA). Our results demonstrated higher levels of neuroinflammation and apoptosis markers when NPCs were cultured in the amyloid-like matrix compared to a natural brain matrix. Here, we provided insights into the impact of amyloid-like structures on NPC phenotypes and behaviors. This foundational work, before progressing to more complex plaque models, provides a promising scaffold for future investigations on AD mechanisms and drug testing. STATEMENT OF SIGNIFICANCE: In this study, we engineered two multi-component hydrogels: one to mimic the natural extracellular matrix (ECM) of the brain and one to resemble an amyloid-like microenvironment using a self-assembling peptide hydrogel. The self-assembling peptide mimics β-amyloid fibrils seen in amyloid-β protein aggregates. We report on the culture of neuronal progenitor cells within the amyloid-mimicking ECM scaffold to study the impact through marker expressions related to inflammation and DNA damage. This foundational work, before progressing to more complex plaque models, offers a promising scaffold for future investigations on AD mechanisms and drug testing.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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