@article{55d0d31ec70f4b98aa9a4a96588d1795,
title = "Artificial extracellular matrix scaffolds of mobile molecules enhance maturation of human stem cell-derived neurons",
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.",
keywords = "IKVAV, dynamics, extracellular matrix, iPSC-derived neurons, laminin, neuronal maturation, peptide amphiphiles, supramolecular motion, supramolecular nanofibers",
author = "Zaida {\'A}lvarez and Ortega, {J. Alberto} and Kohei Sato and Sasselli, {Ivan R.} and Kolberg-Edelbrock, {Alexandra N.} and Ruomeng Qiu and Marshall, {Kelly A.} and Nguyen, {Thao Phuong} and Smith, {Cara S.} and Quinlan, {Katharina A.} and Vasileios Papakis and Zois Syrgiannis and Sather, {Nicholas A.} and Chiara Musumeci and Elisabeth Engel and Stupp, {Samuel I.} and Evangelos Kiskinis",
note = "Funding Information: We are grateful to the following funding sources: US National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) and NIH National Institute on Aging R01NS104219 (E.K.), the Les Turner ALS Foundation (E.K.), the New York Stem Cell Foundation (E.K.), the NIH National Institute of Biomedical Imaging and Bioengineering 5R01EB003806 (S.I.S.), NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health R01AR0727 (S.I.S.), the Center for Regenerative Nanomedicine at the Simpson Querrey Institute (S.I.S.), US Department of Energy DE-SC0001329 (S.I.S.), grant PID2021-124839OA-I00 and PID2020-114407RA-I00 funded by MCIN/AEI/10.13039/501100011033 (Z.{\'A}. and J.A.O.), Mike Lane fellowship from Castellers de Vila de Gracia 2021 (Z.{\'A}.), AFM-Telethon Trampoline Grant #23648 (J.A.O.), Beatriu de Pinos 2019 BP 00058 (Z.{\'A}.), Ramon y Cajal fellowship RYC2020-028732-I (Z.{\'A}.) and RYC2019-026980-I (J.A.O.), Gipuzkoa Foru Aldundia 2019-FELL-000017-01 and Maria de Maeztu Units of Excellence MDM-2017-0720 (I.R.S.), and NIH NINDS R01 NS104436 (K.A.Q.). We thank the Peptide Synthesis Core Facility and the Analytical BioNanoTechnology Core Facility, supported by the SHyNE Resource (NSFECCS-2025633), the Center for Advanced Molecular Imaging (NCI CCSG P30 CA060553), the Proteomics Core Facility (NCI CCSG P30 CA060553), the National Resource for Translational and Developmental Proteomics (P41 GM108569), the Materials Research Science and Engineering Center (NSFDMR-1720139), the REACT Facility of the Northwestern University Center for Catalysis and Surface Science, Prof. N. Schweitzer for his assistance with the physisorption measurements, the SasView application developed under NSF award DMR-0520547 and under the SINE2020 project (#654000), the Keck Biophysics Facility (grant #P30 CA060553); Northwestern University Center for Advanced Microscopy (NCI CCSG P30 CA060553), the Scanned Probe Imaging and Development, BioCryo, and Micro/Nano Fabrication facilities of NU's NUANCE Center (NSFECCS-2025633), the IIN and Northwestern's MRSEC program (NSFDMR-1720139), the IBEC Core Facility and Microscopy Characterization Facility, and Unit 7 of ICTS “NANBIOSIS” from CIBER-BBN both at Institute for Bioengineering of Catalonia. We thank M. Ziller for assisting with gene expression analysis and M. Seniw for the preparation of graphic illustrations. E.K. is a New York Stem Cell Foundation—Robertson Investigator. Conceptualization, Z.{\'A}. J.A.O. K.S. S.I.S. and E.K.; methodology, Z.{\'A}. J.A.O. K.S. and I.R.S.; formal analysis, Z.{\'A}. J.A.O. and K.S.; validation, T.P.N. and C.S.S.; formal analysis, Z.{\'A}. J.A.O. K.S. I.R.S. R.Q. K.A.M. T.P.N. K.A.Q. Z.S. N.A.S. and C.M.; investigation, Z.{\'A}. J.A.O. K.S. I.R.S. A.N.K.-E. R.Q. K.A.M. T.P.N. C.S.S. K.A.Q. Z.S. N.A.S. C.M. and V.P.; resources, Z.{\'A}. J.A.O. E.E. S.I.S. and E.K.; writing – original draft, Z.{\'A}. J.A.O. K.S. S.I.S. and E.K.; writing – review & editing, Z.{\'A}. J.A.O. K.S. I.R.S. A.N.K.-E. R.Q. K.A.M. T.P.N. C.S.S. K.A.Q. Z.S. N.A.S. C.M. E.E. S.I.S. and E.K.; visualization, Z.{\'A}. and J.A.O.; supervision, S.I.S. and E.K.; project administration, S.I.S. and E.K.; funding acquisition, Z.{\'A}. J.A.O. S.I.S. and E.K. A patent pertaining to this work has been filed and is pending: “Dynamics Within Supramolecular IKVAV Matrices Enhance Functional Maturation of hiPSC-Derived Neurons and Regeneration” (inventors: Z.{\'A}. J.A.O. K.S. E.K. and S.I.S.). E.K. N.A.S. and S.I.S. are co-founders of NeuronGrow. Funding Information: We are grateful to the following funding sources: US National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) and NIH National Institute on Aging R01NS104219 (E.K.), the Les Turner ALS Foundation (E.K.), the New York Stem Cell Foundation (E.K.), the NIH National Institute of Biomedical Imaging and Bioengineering 5R01EB003806 (S.I.S.), NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health R01AR0727 (S.I.S.), the Center for Regenerative Nanomedicine at the Simpson Querrey Institute (S.I.S.), US Department of Energy DE-SC0001329 (S.I.S.), grant PID2021-124839OA-I00 and PID2020-114407RA-I00 funded by MCIN/AEI/10.13039 / 501100011033 (Z.{\'A}. and J.A.O.), Mike Lane fellowship from Castellers de Vila de Gracia 2021 (Z.{\'A}.), AFM-Telethon Trampoline Grant # 23648 (J.A.O.), Beatriu de Pinos 2019 BP 00058 (Z.{\'A}.), Ramon y Cajal fellowship RYC2020-028732-I (Z.{\'A}.) and RYC2019-026980-I (J.A.O.), Gipuzkoa Foru Aldundia 2019-FELL-000017-01 and Maria de Maeztu Units of Excellence MDM-2017-0720 (I.R.S.), and NIH NINDS R01 NS104436 (K.A.Q.). We thank the Peptide Synthesis Core Facility and the Analytical BioNanoTechnology Core Facility, supported by the SHyNE Resource ( NSF ECCS-2025633 ), the Center for Advanced Molecular Imaging ( NCI CCSG P30 CA060553 ), the Proteomics Core Facility ( NCI CCSG P30 CA060553 ), the National Resource for Translational and Developmental Proteomics ( P41 GM108569 ), the Materials Research Science and Engineering Center ( NSF DMR-1720139 ), the REACT Facility of the Northwestern University Center for Catalysis and Surface Science , Prof. N. Schweitzer for his assistance with the physisorption measurements, the SasView application developed under NSF award DMR-0520547 and under the SINE2020 project (# 654000 ), the Keck Biophysics Facility (grant # P30 CA060553 ); Northwestern University Center for Advanced Microscopy ( NCI CCSG P30 CA060553 ), the Scanned Probe Imaging and Development, BioCryo, and Micro/Nano Fabrication facilities of NU{\textquoteright}s NUANCE Center ( NSF ECCS-2025633 ), the IIN and Northwestern's MRSEC program ( NSF DMR-1720139 ), the IBEC Core Facility and Microscopy Characterization Facility, and Unit 7 of ICTS “NANBIOSIS” from CIBER-BBN both at Institute for Bioengineering of Catalonia. We thank M. Ziller for assisting with gene expression analysis and M. Seniw for the preparation of graphic illustrations. E.K. is a New York Stem Cell Foundation—Robertson Investigator. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2023",
month = feb,
day = "2",
doi = "10.1016/j.stem.2022.12.010",
language = "English (US)",
volume = "30",
pages = "219--238.e14",
journal = "Cell stem cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "2",
}
