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Photoresponsive Hydrogels with Photoswitchable Stiffness: Emerging Platforms to Study Temporal Aspects of Mesenchymal Stem Cell Responses to Extracellular Stiffness Regulation

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Cell Biology and Translational Medicine, Volume 5

Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1144))

Abstract

An extensive number of cell-matrix interaction studies have identified matrix stiffness as a potent regulator of cellular properties and behaviours. Perhaps most notably, matrix stiffness has been demonstrated to regulate mesenchymal stem cell (MSC) phenotype and lineage commitment. Given the therapeutic potential for MSCs in regenerative medicine, significant efforts have been made to understand the molecular mechanisms involved in stiffness regulation. These efforts have predominantly focused on using stiffness-defined polyacrylamide (PA) hydrogels to culture cells in 2D and have enabled elucidation of a number of mechano-sensitive signalling pathways. However, despite proving to be a valuable tool, these stiffness-defined hydrogels do not reflect the dynamic nature of living tissues, which are subject to continuous remodelling during processes such as development, ageing, disease and regeneration. Therefore, in order to study temporal aspects of stiffness regulation, researchers have developed and exploited novel hydrogel substrates with in situ tuneable stiffness. In particular, photoresponsive hydrogels with photoswitchable stiffness are emerging as exciting platforms to study MSC stiffness regulation. This chapter provides an introduction to the use of PA hydrogel substrates, the molecular mechanisms of mechanotransduction currently under investigation and the development of these emerging photoresponsive hydrogel platforms.

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Abbreviations

MSC:

Mesenchymal stem cell

ECM:

Extracellular matrix

BMPs:

Bone morphogenic proteins

TGF-β:

Transforming growth factor beta

PA:

Polyacrylamide

IAC:

Integrin adhesion complex

FA:

Focal adhesion

MAPK1:

Mitogen-activated protein kinase 1

LIM:

LIN-11, ISl1 and MEC-3

NMII:

Non-muscle myosin-II

RhoA:

Ras homolog gene family, member A

ROCK:

Rho-associated protein kinase

YAP:

Yes-associated protein

TAZ:

Transcriptional coactivator with PDZ-binding motif

LINC:

Linker of nucleo- and cytoskeleton

MKL1:

myocardin-like protein 1

RUNX2:

Runt-related transcription factor 2

SRF:

Serum response factor

PEG:

Poly(ethylene glycol)

PEGdiPDA:

Photodegradable PEG diacrylate

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Acknowledgements

D.R. was supported by the EPSRC & MRC funded Centre for Doctoral Training in Regenerative Medicine (EP/L014904/1). J.S. was funded by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/L024551/1).

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Authors and Affiliations

  1. Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

    David Richards, Joe Swift & Stephen M. Richardson

  2. Wellcome Trust Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

    Joe Swift

  3. Manchester Institute of Biotechnology and School of Chemistry, University of Manchester, Manchester, UK

    Lu Shin Wong

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  1. David Richards
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Correspondence to Stephen M. Richardson .

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  1. (Retired), Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Kursad Turksen

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Richards, D., Swift, J., Wong, L.S., Richardson, S.M. (2018). Photoresponsive Hydrogels with Photoswitchable Stiffness: Emerging Platforms to Study Temporal Aspects of Mesenchymal Stem Cell Responses to Extracellular Stiffness Regulation. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 5. Advances in Experimental Medicine and Biology(), vol 1144. Springer, Cham. https://doi.org/10.1007/5584_2018_293

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