title: Mimicking normal tissue architecture and perturbation in cancer with engineered micro-epidermis.
abstract: 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 μm 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 μm 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.
authors.affiliation: Melville Laboratory for Polymer Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
authors.forename: Julien E
authors.initials: JE
authors.lastname: Gautrot
authors.forename: Chunming
authors.initials: C
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Goldie
authors.forename: Britta
authors.initials: B
authors.lastname: Trappmann
authors.forename: Wilhelm T S
authors.initials: WT
authors.lastname: Huck
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Watt
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D003896:Desmosomes / Q000378:metabolism; D004817:Epidermis / Q000502:physiology*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000473:pathology*; D017768:Skin, Artificial; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D015820:Cadherins