Laminin and biomimetic extracellular elasticity enhance functional differentiation in mammary epithelia This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.Thislicensedoesnot permit commercial exploitation or the creation of derivative works without specific permission.

TLDR: In the mammary gland, epithelial cells are embedded in a soft environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel as discussed by the authors.

Abstract: In the mammary gland, epithelial cells are embedded in a ‘soft’ environment and become functionally differentiated in culture when exposed to a laminin-rich extracellular matrix gel. Here, we def ine the processes by which mammary epithelial cells integrate biochemical and mechanical extracellular cues to maintain their differentiated phenotype. We used single cells cultured on top of gels in conditions permissive for b-casein expression using atomic force microscopy to measure the elasticity of the cells and their underlying substrata. We found that maintenance of b-casein expression required both laminin signalling and a ‘soft’ extracellular matrix, as is the case in normal tissues in vivo ,a nd biomimetic intracellular elasticity, as is the case in primary mammary epithelial organoids. Conversely, two hallmarks of breast cancer development, stiffening of the extracellular matrix and loss of laminin signalling, led to the loss of bcasein expression and non-biomimetic intracellular elasticity. Our data indicate that tissue-specific gene expression is controlled by both the tissues’ unique biochemical milieu and mechanical properties, processes involved in maintenance of