Instructing cells with programmable peptide DNA hybrids

Ronit Freeman, Nicholas Stephanopoulos, Zaida Álvarez, Jacob A Lewis, Shantanu Sur, Chris M Serrano, Job Boekhoven, Sungsoo S. Lee and Samuel I. Stupp ()
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Ronit Freeman: Simpson Querrey Institute for BioNanotechnology, Northwestern University
Nicholas Stephanopoulos: Simpson Querrey Institute for BioNanotechnology, Northwestern University
Zaida Álvarez: Simpson Querrey Institute for BioNanotechnology, Northwestern University
Jacob A Lewis: Northwestern University
Shantanu Sur: Simpson Querrey Institute for BioNanotechnology, Northwestern University
Chris M Serrano: Northwestern University
Job Boekhoven: Simpson Querrey Institute for BioNanotechnology, Northwestern University
Sungsoo S. Lee: Simpson Querrey Institute for BioNanotechnology, Northwestern University
Samuel I. Stupp: Simpson Querrey Institute for BioNanotechnology, Northwestern University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15982

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