Cells work together to ‘feel’ materials for better tissue regeneration

Science Building Seminar room - SB036
11am

C.G. Tusan (Centre for Human Development, Stem Cells and Regeneration, University of Southampton)

Regenerative medicine aims to restore damaged tissues and organs. Aside from chemical cues, cells can sense the mechanical properties of the extracellular matrix (ECM). An increase in stiffness is known to affect the growth and differentiation of individual cells, but the mechanism by which groups of cells respond to stiffness is poorly understood [1]. In this study, we tested the hypothesis that groups of cells, working together, exert more force and deform matrices more than single cells do. This allows them to mechanosense at longer range than individual cells.
To achieve this, we developed polyacrylamide (PA) hydrogels attached to glass substrates that vary in stiffness and in thickness. MG63 bone cells were seeded on soft PA gels (1kPa) with variable thickness (0 - 200 μm) and allowed to form colonies for 5 days. Cell spreading and deformations of fluorescent microspheres embedded in PA were obtained using time- lapse fluorescence microscopy imaging.
Our results show that as hydrogel thickness increases, single cell spreading decreases, and the data can be fit to an exponential model characterized by a half-maximal response of 3.2 μm. Similarly, we found that colony spreading decreases with increasing hydrogel thickness, but with a greater half-maximum response of 54 μm. Moreover, hydrogel deformations were significantly greater (p<0.05) and extended great distances on thick hydrogels compared to thin hydrogels. Also, on thick gels colonies exhibit longer and more frequent cytoplasmic extensions, which were identified to promote coalescence of colonies.
Our data suggest that cells act collectively to detect tissue mechanics and that they are able to feel through materials - like the proverbial “princess and the pea”. This implies that colonies or layers of cells may be able to detect material properties at comparatively large distances. Our findings may be relevant for the design of material implants to help cure disease, and to understand how cancer progresses or body heals and develops.

Acknowledgements
We gratefully acknowledge the support and generosity of Rosetrees Trust and Wessex Medical Research for funding this project.

References :

[1]  N.D. Evans, J. Mater. Chem. B 2 (17), 2345-2356 (2014)

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