@article {661,
	title = {Multicellular architecture of malignant breast epithelia influences mechanics.},
	journal = {PLoS One},
	volume = {9},
	year = {2014},
	month = {2014},
	pages = {e101955},
	abstract = {<p>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.</p>
},
	issn = {1932-6203},
	doi = {10.1371/journal.pone.0101955},
	author = {Venugopalan, Gautham and Camarillo, David B and Webster, Kevin D and Reber, Clay D and Sethian, James A and Weaver, Valerie M and Fletcher, Daniel A and El-Samad, Hana and Rycroft, Chris H}
}
@article {241,
	title = {Rapid disorganization of mechanically interacting systems of mammary acini.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {111},
	year = {2014},
	month = {2014 Jan 14},
	pages = {658-63},
	abstract = {<p>Cells and multicellular structures can mechanically align and concentrate fibers in their ECM environment and can sense and respond to mechanical cues by differentiating, branching, or disorganizing. Here we show that mammary acini with compromised structural integrity can interconnect by forming long collagen lines. These collagen lines then coordinate and accelerate transition to an invasive phenotype. Interacting acini begin to disorganize within 12.5 \&plusmn; 4.7 h in a spatially coordinated manner, whereas acini that do not interact mechanically with other acini disorganize more slowly (in 21.8 \&plusmn; 4.1 h) and to a lesser extent (P \&lt; 0.0001). When the directed mechanical connections between acini were cut with a laser, the acini reverted to a slowly disorganizing phenotype. When acini were fully mechanically isolated from other acini and also from the bulk gel by box-cuts with a side length \&lt;900 μm, transition to an invasive phenotype was blocked in 20 of 20 experiments, regardless of waiting time. Thus, pairs or groups of mammary acini can interact mechanically over long distances through the collagen matrix, and these directed mechanical interactions facilitate transition to an invasive phenotype.</p>
},
	keywords = {Acinar Cells, Breast Neoplasms, Cell Communication, Cell Line, Tumor, Cell Separation, Collagen, Escherichia coli, Female, Humans, Kaplan-Meier Estimate, Mammary Glands, Human, Microscopy, Atomic Force, Microscopy, Electron, Scanning, Microscopy, Fluorescence},
	issn = {1091-6490},
	doi = {10.1073/pnas.1311312110},
	author = {Shi, Quanming and Ghosh, Rajarshi P and Engelke, Hanna and Rycroft, Chris H and Cassereau, Luke and Sethian, James A and Weaver, Valerie M and Liphardt, Jan T}
}
