Volume 22, Issue 10 p. 1755-1760
Communication

Reversible Control of Gelatin Hydrogel Stiffness by Using DNA Crosslinkers**

Alex Buchberger

Alex Buchberger

School of Molecular Sciences, Arizona State University, P.O. Box 877301, Tempe, AZ 85287 USA

Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281 USA

These authors contributed equally to this work.

Search for more papers by this author
Harpinder Saini

Harpinder Saini

School of Biological and Health Systems Engineering, Arizona State University, 501 E. Tyler mall, ECG 334A, Tempe AZ, 85287 USA

Virginia G. Piper Center for Personalized Diagnostics The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe AZ, 85281 USA

These authors contributed equally to this work.

Search for more papers by this author
Kiarash Rahmani Eliato

Kiarash Rahmani Eliato

Department of Physics, Arizona State University, 550 E Tyler Drive, Tempe, AZ 85287 USA

Center for Biological Physics, Arizona State University, P.O. Box 871504, Tempe, AZ, 85287 USA

Center for Single Molecule Biophysics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281 USA

These authors contributed equally to this work.

Search for more papers by this author
Azadeh Zare

Azadeh Zare

Department of Physics, Arizona State University, 550 E Tyler Drive, Tempe, AZ 85287 USA

Center for Biological Physics, Arizona State University, P.O. Box 871504, Tempe, AZ, 85287 USA

Center for Single Molecule Biophysics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281 USA

Search for more papers by this author
Ryan Merkley

Ryan Merkley

School of Molecular Sciences, Arizona State University, P.O. Box 877301, Tempe, AZ 85287 USA

Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281 USA

Search for more papers by this author
Yang Xu

Yang Xu

School of Molecular Sciences, Arizona State University, P.O. Box 877301, Tempe, AZ 85287 USA

Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281 USA

Search for more papers by this author
Julio Bernal

Julio Bernal

School of Molecular Sciences, Arizona State University, P.O. Box 877301, Tempe, AZ 85287 USA

Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281 USA

Search for more papers by this author
Robert Ros

Corresponding Author

Robert Ros

Department of Physics, Arizona State University, 550 E Tyler Drive, Tempe, AZ 85287 USA

Center for Biological Physics, Arizona State University, P.O. Box 871504, Tempe, AZ, 85287 USA

Center for Single Molecule Biophysics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281 USA

Search for more papers by this author
Mehdi Nikkhah

Corresponding Author

Mehdi Nikkhah

School of Biological and Health Systems Engineering, Arizona State University, 501 E. Tyler mall, ECG 334A, Tempe AZ, 85287 USA

Virginia G. Piper Center for Personalized Diagnostics The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe AZ, 85281 USA

Search for more papers by this author
Dr. Nicholas Stephanopoulos

Corresponding Author

Dr. Nicholas Stephanopoulos

School of Molecular Sciences, Arizona State University, P.O. Box 877301, Tempe, AZ 85287 USA

Center for Molecular Design and Biomimetics, The Biodesign Institute, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ 85281 USA

Search for more papers by this author
First published: 23 January 2021
Citations: 12
**

A previous version of this manuscript has been deposited on a preprint server (https://chemrxiv.org/articles/preprint/Reversible_Control_of_Gelatin_Hydrogel_Stiffness_Using_DNA_Crosslinkers/12461918/1)

Graphical Abstract

Going soft: We report a gelatin methacrylate hydrogel crosslinked with DNA. The stiffness of the gel can be switched by a factor of ∼2, over two cycles, by using displacement strands, with no degradation of gel performance. Using two DNA sequences allows orthogonal control of gel stiffness and ligand presentation.

Abstract

Biomaterials with dynamically tunable properties are critical for a range of applications in regenerative medicine and basic biology. In this work, we show the reversible control of gelatin methacrylate (GelMA) hydrogel stiffness through the use of DNA crosslinkers. We replaced some of the inter-GelMA crosslinks with double-stranded DNA, allowing for their removal through toehold-mediated strand displacement. The crosslinks could be restored by adding fresh dsDNA with complementary handles to those on the hydrogel. The elastic modulus (G’) of the hydrogels could be tuned between 500 and 1000 Pa, reversibly, over two cycles without degradation of performance. By functionalizing the gels with a second DNA strand, it was possible to control the crosslink density and a model ligand in an orthogonal fashion with two different displacement strands. Our results demonstrate the potential for DNA to reversibly control both stiffness and ligand presentation in a protein-based hydrogel, and will be useful for teasing apart the spatiotemporal behavior of encapsulated cells.