Modulation of corneal tissue mechanics influences epithelial cell phenotype

Ricardo M. Gouveia, Guillaume Lepert, Suneel Gupta, Rajiv R. Mohan, Carl Paterson and Che J. Connon

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Jul 27, 2018
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Received: 8th June 18

The influence of substrate compliance on cell behaviour in vivo remains largely unexplored due to difficulties in evaluating live tissue biomechanics. This study addresses this challenge by using the non-contact Brillouin spectro-microscopy technique to characterise the mechanical properties of the human cornea. The resulting high-resolution analysis of the live corneal tissue revealed that its outer edge (limbus) has a significantly lower bulk modulus compared to the centre, and that this difference is precisely associated with limbal epithelial stem cell (LESC) residence. The strong correlation between tissue compliance and LESC phenotype thus facilitated the formulation of a new therapeutic strategy, whereby stem cell behaviour can be regulated solely through in situ modulation of tissue biomechanics. Specifically, we demonstrated that, following an alkali burn, treating the cornea with collagenase effectively restores the tissues’ capacity to support LESCs both in vivo and ex vivo. These results indicate that substrate stiffness plays a fundamental role in directing cell behaviour across the corneal surface, with modulation of cell phenotype made possible via creation of suitable biomechanical niches in both healthy and wounded tissue. These findings therefore have extended implications for understanding stem cell niche biomechanics and its impact on tissue regeneration.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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Nature Communications

Nature Research, Springer Nature

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