@article{c2a36c0076a046ac9925218a9ba19d9f,
title = "Bioactive scaffolds with enhanced supramolecular motion promote recovery from spinal cord injury",
abstract = "The signaling of cells by scaffolds of synthetic molecules that mimic proteins is known to be effective in the regeneration of tissues. Here, we describe peptide amphiphile supramolecular polymers containing two distinct signals and test them in a mouse model of severe spinal cord injury. One signal activates the transmembrane receptor b1-integrin and a second one activates the basic fibroblast growth factor 2 receptor. By mutating the peptide sequence of the amphiphilic monomers in nonbioactive domains, we intensified the motions of molecules within scaffold fibrils. This resulted in notable differences in vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery. We hypothesize that the signaling of cells by ensembles of molecules could be optimized by tuning their internal motions.",
author = "Z. {\'A}lvarez and Kolberg-Edelbrock, {A. N.} and Sasselli, {I. R.} and Ortega, {J. A.} and R. Qiu and Z. Syrgiannis and Mirau, {P. A.} and F. Chen and Chin, {S. M.} and S. Weigand and E. Kiskinis and Stupp, {S. I.}",
note = "Funding Information: The experimental work and simulations were supported by the Louis A. Simpson and Kimberly K. Querrey Center for Regenerative Nanomedicine at the Simpson Querrey Institute for BioNanotechnology (S.I.S.). Work on NMR analysis was supported by the Air Force Research Laboratory under agreement no. FA8650-15-2-5518. Part of the biological experiments reported here was supported by the National Institute on Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA) R01NS104219 (E.K.), NIH/NINDS grants R21NS107761 and R21NS107761-01A1 (E.K.), the Les Turner ALS Foundation (E.K.), and the New York Stem Cell Foundation (E.K.). We thank the Paralyzed Veterans of America (PVA) Research Foundation PVA17RF0008 (Z.A.), the National Science Foundation (A.N.K.-E. and S.M.C.), and the French Muscular Dystrophy Association (J.A.O.) for graduate and postdoctoral fellowships. We thank the Peptide Synthesis Core and the Analytical Bionanotechnology Equipment Core at the Simpson Querrey Institute for Bionanotechnology for biological and chemical analyses. These facilities have support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS - 1542205). Imaging work was performed at the Center for Advanced Microscopy, and CD measurements were performed at the Northwestern University Keck Biophysics facility. Both of these facilities are generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. Spinning disk confocal microscopy was performed on an Andor XDI revolution microscope, purchased through the support of NCRR 1S10 RR031680-01. Multiphoton microscopy was performed on a Nikon A1R multiphoton microscope, acquired with support from NIH 1S10OD010398-01. Tissue processing was performed at the Pathology Core Facility supported by NCI CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. Electron microscopy experiments were performed at the Electron Probe Instrumentation Center (EPIC) and the BioCryo facility of Northwestern University's NUANCE Center, both of which have received support from the SHyNE Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. NMR and Fourier transform infrared spectroscopy characterization in this work made use of IMSERC at Northwestern University, which has received support from the SHyNE Resource (NSF ECCS-1542205), the State of Illinois, and IIN. Portions of this work were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, The Dow Chemical Company, and DuPont de Nemours, Inc. This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under contract no. DE-AC02-06CH11357. E.K. is a Les Turner ALS Research Center Investigator and a New York Stem Cell Foundation-Robertson Investigator. Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works",
year = "2021",
month = nov,
day = "12",
doi = "10.1126/science.abh3602",
language = "English (US)",
volume = "374",
pages = "848--856",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6569",
}