Publications

@article{Ashworth2020-so,

title = {Peptide gels of fully-defined composition and mechanics for 

 probing cell-cell and cell-matrix interactions in vitro},

author = {J C Ashworth and J L Thompson and J R James and C E Slater and S Pijuan-Galit\'{o} and K Lis-Slimak and R J Holley and K A Meade and A Thompson and K P Arkill and M Tassieri and A J Wright and G Farnie and C L R Merry},

year  = {2020},

date = {2020-01-01},

journal = {Matrix Biol.},

volume = {85-86},

pages = {15\textendash33},

publisher = {Elsevier BV},

abstract = {Current materials used for in vitro 3D cell culture are often 

 limited by their poor similarity to human tissue, batch-to-batch 

 variability and complexity of composition and manufacture. Here, 

 we present a ``blank slate'' culture environment based on a 

 self-assembling peptide gel free from matrix motifs. The gel can 

 be customised by incorporating matrix components selected to 

 match the target tissue, with independent control of mechanical 

 properties. Therefore the matrix components are restricted to 

 those specifically added, or those synthesised by encapsulated 

 cells. The flexible 3D culture platform provides full control 

 over biochemical and physical properties, allowing the impact of 

 biochemical composition and tissue mechanics to be separately 

 evaluated in vitro. Here, we demonstrate that the peptide gels 

 support the growth of a range of cells including human induced 

 pluripotent stem cells and human cancer cell lines. Furthermore, 

 we present proof-of-concept that the peptide gels can be used to 

 build disease-relevant models. Controlling the peptide gelator 

 concentration allows peptide gel stiffness to be matched to 

 normal breast (1 kPa), with higher stiffness favouring the 

 viability of breast cancer cells over normal breast cells. In 

 parallel, the peptide gels may be modified with matrix 

 components relevant to human breast, such as collagen I and 

 hyaluronan. The choice and concentration of these additions 

 affect the size, shape and organisation of breast epithelial 

 cell structures formed in co-culture with fibroblasts. This 

 system therefore provides a means of unravelling the individual 

 influences of matrix, mechanical properties and cell-cell 

 interactions in cancer and other diseases.},

keywords = {biomaterials, Cancer, extracellular matrix, Stem cells, Stiffness},

pubstate = {published},

tppubtype = {article}

}