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Title: Physical and biological regulation of neuron regenerative growth and network formation on recombinant dragline silks

Journal Article · · Biomaterials
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  1. Tufts Univ., Medford, MA (United States). Dept. of Biomedical Engineering
  2. Utah State Univ., Logan, UT (United States). Dept. of Biology

In this paper, recombinant spider silks produced in transgenic goat milk were studied as cell culture matrices for neuronal growth. Major ampullate spidroin 1 (MaSp1) supported neuronal growth, axon extension and network connectivity, with cell morphology comparable to the gold standard poly-lysine. In addition, neurons growing on MaSp1 films had increased neural cell adhesion molecule (NCAM) expression at both mRNA and protein levels. The results indicate that MaSp1 films present useful surface charge and substrate stiffness to support the growth of primary rat cortical neurons. Moreover, a putative neuron-specific surface binding sequence GRGGL within MaSp1 may contribute to the biological regulation of neuron growth. These findings indicate that MaSp1 could regulate neuron growth through its physical and biological features. Finally, this dual regulation mode of MaSp1 could provide an alternative strategy for generating functional silk materials for neural tissue engineering.

Research Organization:
Utah State Univ., Logan, UT (United States); Tufts Univ., Medford, MA (United States)
Sponsoring Organization:
USDOE Office of Science (SC): National Institutes of Health (NIH); USDOE
Grant/Contract Number:
SC0004791; IIP-1318194; R01 EB014283; P41 EB002520; R01 EY020856
OSTI ID:
1344119
Alternate ID(s):
OSTI ID: 1365582
Journal Information:
Biomaterials, Vol. 48; ISSN 0142-9612
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 33 works
Citation information provided by
Web of Science

References (57)

New perspectives in cell adhesion: RGD and integrins journal October 1987
Isolation of a clone encoding a second dragline silk fibroin. Nephila clavipes dragline silk is a two-protein fiber. journal September 1992
Enhanced neurite growth from mammalian neurons in three-dimensional salmon fibrin gels journal April 2007
Nanocomposites of poly(vinylidene fluoride) with multiwalled carbon nanotubes journal March 2010
Native-sized recombinant spider silk protein produced in metabolically engineered Escherichia coli results in a strong fiber journal July 2010
Nephila clavipes Flagelliform Silk-Like GGX Motifs Contribute to Extensibility and Spacer Motifs Contribute to Strength in Synthetic Spider Silk Fibers journal May 2013
Combining flagelliform and dragline spider silk motifs to produce tunable synthetic biopolymer fibers journal October 2011
Regulators of Neurite Outgrowth: Role of Cell Adhesion Molecules journal April 2004
The structure and properties of spider silk journal January 1986
Untangling spider silk evolution with spidroin terminal domains journal January 2010
Matrices with Compliance Comparable to that of Brain Tissue Select Neuronal over Glial Growth in Mixed Cortical Cultures journal April 2006
An Essential Role for the C-Terminal Domain of A Dragline Spider Silk Protein in Directing Fiber Formation journal June 2006
Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth journal April 2005
Arg-Gly-Asp: A versatile cell recognition signal journal February 1986
The Collagen-binding A-domains of Integrins α 1 β 1 and α 2 β 1 Recognize the Same Specific Amino Acid Sequence, GFOGER, in Native (Triple-helical) Collagens journal January 2000
Binding properties of a cell adhesion molecule from neural tissue. journal January 1982
Strength in the Periphery: Growth Cone Biomechanics and Substrate Rigidity Response in Peripheral and Central Nervous System Neurons journal February 2012
The treatment of TBI with human marrow stromal cells impregnated into collagen scaffold: Functional outcome and gene expression profile journal January 2011
Structural characterization of a homophilic binding site in the neural cell adhesion molecule. journal September 1993
Silk Hydrogels as Soft Substrates for Neural Tissue Engineering journal April 2013
Hypotheses that correlate the sequence, structure, and mechanical properties of spider silk proteins journal March 1999
Liquid crystalline spinning of spider silk journal March 2001
Differential distribution of aggrecan isoforms in perineuronal nets of the human cerebral cortex journal February 2009
Bioengineered sequential growth factor delivery stimulates brain tissue regeneration after stroke journal November 2013
Film-Based Implants for Supporting Neuron-Electrode Integrated Interfaces for The Brain journal November 2013
Charge-Tunable Autoclaved Silk-Tropoelastin Protein Alloys That Control Neuron Cell Responses journal March 2013
A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery journal November 2011
Inducing β-Sheets Formation in Synthetic Spider Silk Fibers by Aqueous Post-Spin Stretching journal June 2011
Reproducing Natural Spider Silks’ Copolymer Behavior in Synthetic Silk Mimics journal November 2012
Regenerative potential of silk conduits in repair of peripheral nerve injury in adult rats journal January 2012
Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration journal December 2006
An Engineered α1 Integrin-binding Collagenous Sequence journal October 2010
Ankyrin binding activity shared by the neurofascin/L1/NrCAM family of nervous system cell adhesion molecules. journal November 1994
Making recombinant extracellular matrix proteins journal May 2008
Stem cell-based tissue engineering with silk biomaterials journal December 2006
Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep journal February 2011
Design and Characterization of a Synthetically Accessible, Photodegradable Hydrogel for User-Directed Formation of Neural Networks journal June 2014
Recombinant spider silk matrices for neural stem cell cultures journal November 2012
Tunable Self-Assembly of Genetically Engineered Silk–Elastin-like Protein Polymers journal November 2011
Spider dragline silk proteins in transgenic tobacco leaves: accumulation and field production: Spider silk proteins in tobacco journal August 2004
Interactions between Spider Silk and Cells – NIH/3T3 Fibroblasts Seeded on Miniature Weaving Frames journal August 2010
Spider Silk:  Ancient Ideas for New Biomaterials journal September 2006
The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue journal October 2002
Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin journal September 1994
NeurphologyJ: An automatic neuronal morphology quantification method and its application in pharmacological discovery journal January 2011
Structure of a protein superfiber: spider dragline silk. journal September 1990
Spider silk fibres in artificial nerve constructs promote peripheral nerve regeneration journal June 2008
Production of synthetic spider dragline silk protein in Pichia pastoris journal January 1997
The role of terminal domains during storage and assembly of spider silk proteins journal November 2011
The homophilic binding site of the neural cell adhesion molecule NCAM is directly involved in promoting neurite outgrowth from cultured neural retinal cells. journal May 1994
Recombinant spider silk as matrices for cell culture journal December 2010
The influence of specific binding of collagen–silk chimeras to silk biomaterials on hMSC behavior journal January 2013
The Neural Cell Adhesion Molecule NCAM Is an Alternative Signaling Receptor for GDNF Family Ligands journal June 2003
Spider Silk Fibers Spun from Soluble Recombinant Silk Produced in Mammalian Cells journal January 2002
Mechanical and Physical Properties of Recombinant Spider Silk Films Using Organic and Aqueous Solvents journal July 2014
Neural responses to electrical stimulation on patterned silk films: Electrical Stimulation on Patterned Silk Films journal July 2013
Cell adhesion and motility depend on nanoscale RGD clustering journal May 2000

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In vitro bioengineered model of cortical brain tissue journal August 2015
Bioactive Silk‐Based Nerve Guidance Conduits for Augmenting Peripheral Nerve Repair journal September 2018
Intracellular Pathways Involved in Bone Regeneration Triggered by Recombinant Silk-Silica Chimeras journal September 2017
Mimicking the Brain Extracellular Matrix in Vitro : A Review of Current Methodologies and Challenges journal July 2019
Tissue Engineered Neural Constructs Composed of Neural Precursor Cells, Recombinant Spidroin and PRP for Neural Tissue Regeneration journal February 2019
Nerve guidance conduit design based on self-rolling tubes journal January 2020
Biomedical Applications of Recombinant Silk-Based Materials journal February 2018
Effect of Silk Fibroin on Neuroregeneration After Traumatic Brain Injury journal December 2018
Design of Multistimuli Responsive Hydrogels Using Integrated Modeling and Genetically Engineered Silk-Elastin-Like Proteins journal April 2016
Predicting rates of in vivo degradation of recombinant spider silk proteins: Integrated modelling and experimental approach for predicting protein degradation journal May 2017