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 β1-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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Survival
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Computer Simulation
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Human Umbilical Vein Endothelial Cells / physiology
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Humans
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Integrin beta1 / metabolism
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Laminin / chemistry
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Laminin / metabolism
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Mice
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Motor Neurons / physiology
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Nanofibers*
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Neovascularization, Physiologic
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Neural Stem Cells / physiology
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Peptides* / chemistry
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Peptidomimetics / chemistry
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Polymers / chemistry
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Protein Conformation, beta-Strand
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Receptor, Fibroblast Growth Factor, Type 2 / metabolism
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Recovery of Function
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Signal Transduction
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Spinal Cord Injuries / therapy*
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Spinal Cord Regeneration*
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Surface-Active Agents
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Tissue Scaffolds*
Substances
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Integrin beta1
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Itgb1 protein, mouse
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Laminin
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Peptides
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Peptidomimetics
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Polymers
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Surface-Active Agents
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Fgfr2 protein, mouse
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Receptor, Fibroblast Growth Factor, Type 2