Photoresponsive substrates for resolving
mechanobiology in cell migration

Abstract: 

Collective migration is the migration of cells in a group rather than as individual. One of the unique emergent phenotypes that cannot be observed in the single cell level the separation of epithelial cells in leading edge into actively migrating leader cells and follower cells. At the same time, epithelial cells do not always migrate collectively, but change to migrate as individual through epithelial-mesenchymal transition (EMT). These processes are regulated not only by soluble factors, but also by the mechanobiological interplay at the cell-cell and cell-extracellular matrix (ECM) interfaces.

In this talk I will introduce two kinds of photoactivatable substrates designed to decipher such complex regulation mechanisms of collective phenotypes. The first one is photoactivatable interfaces, where poly(ethylene glycol) is conjugated through photocleavable 2-nitrobenzyl ester.[1] By spatiotemporally controlling photoirradiation on the substrate, we can control cellular accessibility to a cell-adhesive peptide co-immobilized on the surface and investigate mechanobiological regulation of the leader cell formation during epithelial sheet expansion.[2] The second one is photoactivatable hydrogels based on a photo-isomerizable azobenzene-containing polymer, where photoinduced phase-transition behaviors of the polymer affect the bulk elasticity of the hydrogel.[3] We applied this gel to investigate the impact of dynamic mechanical change on the EMT marker expression.

 

References

1. J. Nakanishi, Photoactivatable Substrates: A Material-Based Approach for Dissecting Cell Migration [Personal Account], Chem. Rec. 17 (2017) 611-621.

2. S.A. Abdellatef, J. Nakanishi, Photoactivatable substrates for systematic study of the impact of an extracellular matrix ligand on appearance of leader cells in collective cell migration, Biomaterials 169 (2018) 72-84.

3. K. Homma, A. C. Chang, S. Yamamoto, R. Tamate, T. Ueki, J. Nakanishi, Design of azobenzene-bearing hydrogel with photoswitchable mechanics driven by photo-induced phase transition for in vitro disease modeling. Acta Biomater. in press.