Multicellular architecture of malignant breast epithelia influences mechanics.

TitleMulticellular architecture of malignant breast epithelia influences mechanics.
Publication TypeJournal Article
Year of Publication2014
AuthorsVenugopalan G, Camarillo DB, Webster KD, Reber CD, Sethian JA, Weaver VM, Fletcher DA, El-Samad H, Rycroft CH
JournalPLoS One
Date Published2014

Cell-matrix and cell-cell mechanosensing are important in many cellular processes, particularly for epithelial cells. A crucial question, which remains unexplored, is how the mechanical microenvironment is altered as a result of changes to multicellular tissue structure during cancer progression. In this study, we investigated the influence of the multicellular tissue architecture on mechanical properties of the epithelial component of the mammary acinus. Using creep compression tests on multicellular breast epithelial structures, we found that pre-malignant acini with no lumen (MCF10AT) were significantly stiffer than normal hollow acini (MCF10A) by 60%. This difference depended on structural changes in the pre-malignant acini, as neither single cells nor normal multicellular acini tested before lumen formation exhibited these differences. To understand these differences, we simulated the deformation of the acini with different multicellular architectures and calculated their mechanical properties; our results suggest that lumen filling alone can explain the experimentally observed stiffness increase. We also simulated a single contracting cell in different multicellular architectures and found that lumen filling led to a 20% increase in the "perceived stiffness" of a single contracting cell independent of any changes to matrix mechanics. Our results suggest that lumen filling in carcinogenesis alters the mechanical microenvironment in multicellular epithelial structures, a phenotype that may cause downstream disruptions to mechanosensing.

Alternate JournalPLoS ONE
PubMed ID25111489
PubMed Central IDPMC4128597
Grant ListT32CA108462 / CA / NCI NIH HHS / United States
U54CA143836 / CA / NCI NIH HHS / United States