Mimicking normal tissue architecture and perturbation in cancer with engineered micro-epidermis

TY - JOUR

T1 - Mimicking normal tissue architecture and perturbation in cancer with engineered micro-epidermis

AU - Gautrot, Julien E

AU - Wang, Chunming

AU - Liu, Xin

AU - Goldie, Stephen J

AU - Trappmann, Britta

AU - Huck, Wilhelm T S

AU - Watt, Fiona M

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

KW - Adherens Junctions

KW - Animals

KW - Cadherins

KW - Cell Line, Tumor

KW - Cytoskeleton

KW - Desmosomes

KW - Epidermis

KW - Humans

KW - Mice

KW - Neoplasms

KW - Skin, Artificial

KW - Tissue Engineering

U2 - 10.1016/j.biomaterials.2012.04.009

DO - 10.1016/j.biomaterials.2012.04.009

M3 - Article

C2 - 22541538

SN - 0142-9612

VL - 33

SP - 5221

EP - 5229

JO - Biomaterials

JF - Biomaterials

IS - 21

M1 - N/A

ER -