Photoresponsive hydrogels with photoswitchable mechanical properties allow time-resolved analysis of cellular responses to matrix stiffening

Lee, I.-N., Dobre, O. , Richards, D., Ballestrem, C., Curran, J. M., Hunt, J. A., Richardson, S. M., Swift, J. and Wong, L. S. (2018) Photoresponsive hydrogels with photoswitchable mechanical properties allow time-resolved analysis of cellular responses to matrix stiffening. ACS Applied Materials and Interfaces, 10(9), pp. 7765-7776. (doi: 10.1021/acsami.7b18302) (PMID:29430919) (PMCID:PMC5864053)

Abstract

As cell function and phenotype can be directed by the mechanical characteristics of the surrounding matrix, hydrogels have become important platforms for cell culture systems, with properties that can be tuned by external stimuli, such as divalent cations, enzymatic treatment, and pH. However, many of these stimuli can directly affect cell behavior, making it difficult to distinguish purely mechanical signaling events. This study reports on the development of a hydrogel that incorporates photoswitchable cross-linkers, which can reversibly alter their stiffness upon irradiation with the appropriate wavelength of light. Furthermore, this study reports the response of bone-marrow-derived mesenchymal stem cells (MSCs) on these hydrogels that were stiffened systematically by irradiation with blue light. The substrates were shown to be noncytotoxic, and crucially MSCs were not affected by blue-light exposure. Time-resolved analysis of cell morphology showed characteristic cell spreading and increased aspect ratios in response to greater substrate stiffness. This hydrogel provides a platform to study mechanosignaling in cells responding to dynamic changes in stiffness, offering a new way to study mechanotransduction signaling pathways and biological processes, with implicit changes to tissue mechanics, such as development, ageing, and fibrosis.

• Item Type: Articles
• Additional Information: I-N.L. and O.D. were supported by the Leverhulme Trust (RPG-2014-292) and the Wellcome Trust (105610/Z/14/Z), respectively. J.S. was funded by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/L024551/1). Imaging was carried out in Core Facilities at the Wellcome Trust Centre for Cell-Matrix Research (203128/ Z/16/Z).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dobre, Dr Oana
• Authors: Lee, I.-N., Dobre, O., Richards, D., Ballestrem, C., Curran, J. M., Hunt, J. A., Richardson, S. M., Swift, J., and Wong, L. S.
• College/School: College of Science and Engineering > School of Engineering > Biomedical Engineering
• Journal Name: ACS Applied Materials and Interfaces
• Publisher: American Chemical Society
• ISSN: 1944-8244
• ISSN (Online): 1944-8252
• Published Online: 12 February 2018
• Copyright Holders: Copyright © 2018 American Chemical Society
• First Published: First published in ACS Applied Materials and Interfaces 10(9): 7765-7776
• Publisher Policy: Reproduced under a Creative Commons License