Journal
BIOMATERIALS
Volume 33, Issue 21, Pages 5221-5229Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.04.009
Keywords
Polymer brush; Micro-patterning; Keratinocyte; Morphogenesis; Cadherins; Cancer
Funding
- Wellcome Trust
- Cambridge Cancer Centre
- Leverhulme Trust
- MRC
- Gates Cambridge Trust
- TUMIC EU
- Medical Research Council [G0701336] Funding Source: researchfish
- MRC [G0701336] Funding Source: UKRI
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Correct tissue architecture is essential for normal physiology, yet there have been few attempts to recreate tissues using micro-patterning. We have used polymer brush micro-engineering to generate a stratified micro-epidermis with fewer than 10 human keratinocytes. Epidermal stem cells are captured on 100 mu m diameter circular collagen-coated disks. Within 24 h they assemble a stratified micro-tissue, in which differentiated cells have a central suprabasal location. For rings with a non-adhesive centre of up to 40 mu m diameter, cell-cell and cell-matrix adhesive interactions together result in correct micro-epidermis assembly. Assembly requires actin polymerization, adherens junctions and desmosomes, but not myosin II-mediated contractility nor coordinated cell movement. Squamous cell carcinoma cells on micro-patterned rings exhibit disturbed architecture that correlates with the characteristics of the original tumours. The micro-epidermis we have generated provides a new platform for screening drugs that modulate tissue assembly, quantifying tissue stratification and investigating the properties of tumour cells. (C) 2012 Elsevier Ltd. All rights reserved.
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