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Title: Instructing cells with programmable peptide DNA hybrids

Journal Article · · Nature Communications
DOI:https://doi.org/10.1038/ncomms15982· OSTI ID:1429073
 [1];  [1];  [1];  [2];  [1];  [3]; ORCiD logo [1];  [1];  [4]
  1. Northwestern Univ., Chicago, IL (United States). Simpson Querrey Inst. for BioNanotechnology
  2. Northwestern Univ., Evanston, IL (United States). Dept. of Biomedical Engineering
  3. Northwestern Univ., Evanston, IL (United States). Dept. of Materials Science and Engineering
  4. Northwestern Univ., Chicago, IL (United States). Simpson Querrey Inst. for BioNanotechnology. Dept. of Medicine; Northwestern Univ., Evanston, IL (United States). Dept. of Biomedical Engineering. Dept. of Materials Science and Engineering. Dept. of Chemistry

The native extracellular matrix is a space in which signals can be displayed dynamically and reversibly, positioned with nanoscale precision, and combined synergistically to control cell function. Here we describe a molecular system that can be programmed to control these three characteristics. In this approach we immobilize peptide-DNA (P-DNA) molecules on a surface through complementary DNA tethers directing cells to adhere and spread reversibly over multiple cycles. The DNA can also serve as a molecular ruler to control the distance-dependent synergy between two peptides. Finally, we use two orthogonal DNA handles to regulate two different bioactive signals, with the ability to independently up- or downregulate each over time. This enabled us to discover that neural stem cells, derived from the murine spinal cord and organized as neurospheres, can be triggered to migrate out in response to an exogenous signal but then regroup into a neurosphere as the signal is removed.

Research Organization:
Northwestern Univ., Evanston, IL (United States); Energy Frontier Research Centers (EFRC) (United States). Center for Bio-Inspired Energy Science (CBES)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); National Science Foundation (NSF); European Molecular Biology Organization (EMBO)
Grant/Contract Number:
FG02-00ER45810; SC0000989; 5R01DE015920; 1F32NS077728-01A1; CCSG P30 CA060553; DGE-1324585; NNCI-1542205; DMR-1121262; ALTF 233-2012
OSTI ID:
1429073
Alternate ID(s):
OSTI ID: 1821885; OSTI ID: 1846797
Journal Information:
Nature Communications, Vol. 8; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 60 works
Citation information provided by
Web of Science

References (47)

Effect of RGD nanospacing on differentiation of stem cells journal April 2013
Temperature-Responsive Cell Culture Surfaces Enable “On−Off” Affinity Control between Cell Integrins and RGDS Ligands journal March 2004
Cell-Material Interactions Revealed Via Material Techniques of Surface Patterning journal August 2013
The effect of heparin-functionalized PEG hydrogels on three-dimensional human mesenchymal stem cell osteogenic differentiation journal January 2007
Regulation of neural progenitor proliferation and survival by  1 integrins journal June 2005
Self-assembly for the synthesis of functional biomaterials journal February 2013
The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function. journal October 1994
A 10-amino acid sequence of fibroblast growth factor 2 is sufficient for its mitogenic activity on neural progenitor cells journal June 1997
Programmable Display of DNA–Protein Chimeras for Controlling Cell–Hydrogel Interactions via Reversible Intermolecular Hybridization journal March 2013
Dynamic Display of Bioactivity through Host-Guest Chemistry journal September 2013
DNA-guided display of proteins and protein ligands for the interrogation of biology journal January 2011
Short Laminin Peptide for Improved Neural Stem Cell Growth journal April 2014
Using Azobenzene-Embedded Self-Assembled Monolayers To Photochemically Control Cell Adhesion Reversibly journal June 2009
Impact of Order and Disorder in RGD Nanopatterns on Cell Adhesion journal March 2009
Synthetic peptide F2A4-K-NS mimics fibroblast growth factor-2 in vitro and is angiogenic in vivo journal May 2006
Defining Single Molecular Forces Required to Activate Integrin and Notch Signaling journal May 2013
DNA-based digital tension probes reveal integrin forces during early cell adhesion journal October 2014
An RGD spacing of 440 nm is sufficient for integrin alpha V beta 3- mediated fibroblast spreading and 140 nm for focal contact and stress fiber formation journal September 1991
The extracellular matrix at a glance journal December 2010
Photoresponsive “Smart Template” via Host–Guest Interaction for Reversible Cell Adhesion journal October 2011
The Extracellular Matrix: Not Just Pretty Fibrils journal November 2009
The RGD containing site of the mouse laminin A chain is active for cell attachment, spreading, migration and neurite outgrowth journal March 1991
Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds journal January 2012
Self-assembled DNA nanostructures for distance-dependent multivalent ligand–protein binding journal June 2008
Engineering the Growth Factor Microenvironment with Fibronectin Domains to Promote Wound and Bone Tissue Healing journal September 2011
Novel Extracellular Matrix Structures in the Neural Stem Cell Niche Capture the Neurogenic Factor Fibroblast Growth Factor 2 from the Extracellular Milieu journal September 2007
Enzyme-triggered cell attachment to hydrogel surfaces journal January 2007
Programmable Cell Adhesion Encoded by DNA Hybridization journal January 2006
Dynamic Interfaces between Cells and Surfaces:  Electroactive Substrates that Sequentially Release and Attach Cells journal December 2003
Photodynamic Control of Bioactivity in a Nanofiber Matrix journal November 2012
The role of the ninth and tenth type III domains of human fibronectin in cell adhesion journal March 1994
Receptor- and heparin-binding domains of basic fibroblast growth factor. journal April 1988
The pull of a cell journal July 2013
Sequence-specific nuclease-mediated release of cells tethered by oligonucleotide phospholipids journal June 2015
β1-Integrin and Integrin Linked Kinase Regulate Astrocytic Differentiation of Neural Stem Cells journal August 2014
A DNA-based molecular probe for optically reporting cellular traction forces journal October 2014
Neurospheres: Insights into neural stem cell biology journal December 2004
Specific β1 integrins mediate adhesion, migration, and differentiation of neural progenitors derived from the embryonic striatum journal September 2004
Bioactive DNA-Peptide Nanotubes Enhance the Differentiation of Neural Stem Cells Into Neurons journal December 2014
Dynamic Display of Bioactivity through Host-Guest Chemistry journal September 2013
Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials journal December 2014
The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis journal March 2002
Near-Infrared Upconversion Controls Photocaged Cell Adhesion journal January 2014
 1 integrins activate a MAPK signalling pathway in neural stem cellsthat contributes to their maintenance journal June 2004
Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers journal February 2004
Neural precursor cell chain migration and division are regulated through different beta1 integrins journal August 1998
A Synthetic Peptide Containing the IKVAV Sequence from the A Chain of Laminin Mediates Cell Attachment, Migration, and Neurite Outgrowth journal September 1989

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Biomedical Applications of DNA‐Based Hydrogels journal November 2019
Emerging applications of peptide–oligonucleotide conjugates: bioactive scaffolds, self-assembling systems, and hybrid nanomaterials journal January 2019
Bioengineering strategies to accelerate stem cell therapeutics journal May 2018
About Chemical Strategies to Fabricate Cell-Instructive Biointerfaces with Static and Dynamic Complexity journal May 2018
3D printing with peptide–polymer conjugates for single-step fabrication of spatially functionalized scaffolds journal January 2019
Programmable Construction of Peptide‐Based Materials in Living Subjects: From Modular Design and Morphological Control to Theranostics journal November 2018
Grafting from a Hybrid DNA–Covalent Polymer by the Hybridization Chain Reaction journal July 2018
Supramolecular Self‐Assembly of DNA with a Cationic Polythiophene: From Polyplexes to Fibers journal February 2019
Biomedical Applications of DNA-Based Hydrogels text January 2019
Manipulating cell fate: dynamic control of cell behaviors on functional platforms journal January 2018