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Title: Instructing cells with programmable peptide DNA hybrids

Abstract

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.

Authors:
 [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
Publication Date:
Research Org.:
Northwestern Univ., Evanston, IL (United States); Energy Frontier Research Centers (EFRC) (United States). Center for Bio-Inspired Energy Science (CBES)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States); National Science Foundation (NSF); European Molecular Biology Organization (EMBO)
OSTI Identifier:
1429073
Grant/Contract Number:  
FG02-00ER45810; SC0000989; 5R01DE015920; 1F32NS077728-01A1; CCSG P30 CA060553; DGE-1324585; NNCI-1542205; DMR-1121262; ALTF 233-2012
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 8; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; bioinspired materials; biomaterials - cells; biomedical materials

Citation Formats

Freeman, Ronit, Stephanopoulos, Nicholas, Alvarez, Zaida, Lewis, Jacob A., Sur, Shantanu, Serrano, Chris M., Boekhoven, Job, Lee, Sungsoo S., and Stupp, Samuel I. Instructing cells with programmable peptide DNA hybrids. United States: N. p., 2017. Web. doi:10.1038/ncomms15982.
Freeman, Ronit, Stephanopoulos, Nicholas, Alvarez, Zaida, Lewis, Jacob A., Sur, Shantanu, Serrano, Chris M., Boekhoven, Job, Lee, Sungsoo S., & Stupp, Samuel I. Instructing cells with programmable peptide DNA hybrids. United States. doi:10.1038/ncomms15982.
Freeman, Ronit, Stephanopoulos, Nicholas, Alvarez, Zaida, Lewis, Jacob A., Sur, Shantanu, Serrano, Chris M., Boekhoven, Job, Lee, Sungsoo S., and Stupp, Samuel I. Mon . "Instructing cells with programmable peptide DNA hybrids". United States. doi:10.1038/ncomms15982. https://www.osti.gov/servlets/purl/1429073.
@article{osti_1429073,
title = {Instructing cells with programmable peptide DNA hybrids},
author = {Freeman, Ronit and Stephanopoulos, Nicholas and Alvarez, Zaida and Lewis, Jacob A. and Sur, Shantanu and Serrano, Chris M. and Boekhoven, Job and Lee, Sungsoo S. and Stupp, Samuel I.},
abstractNote = {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.},
doi = {10.1038/ncomms15982},
journal = {Nature Communications},
number = ,
volume = 8,
place = {United States},
year = {2017},
month = {7}
}

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