title: Rapid disorganization of mechanically interacting systems of mammary acini.
abstract: 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 ± 4.7 h in a spatially coordinated manner, whereas acini that do not interact mechanically with other acini disorganize more slowly (in 21.8 ± 4.1 h) and to a lesser extent (P < 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 <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.
authors.affiliation: Bay Area Physical Sciences Oncology Center and Departments of Physics and Mathematics, University of California, Berkeley, CA 94720.
authors.forename: Quanming
authors.initials: Q
authors.lastname: Shi
authors.forename: Rajarshi P
authors.initials: RP
authors.lastname: Ghosh
authors.forename: Hanna
authors.initials: H
authors.lastname: Engelke
authors.forename: Chris H
authors.initials: CH
authors.lastname: Rycroft
authors.forename: Luke
authors.initials: L
authors.lastname: Cassereau
authors.forename: James A
authors.initials: JA
authors.lastname: Sethian
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Weaver
authors.forename: Jan T
authors.initials: JT
authors.lastname: Liphardt
mesh_terms: D061354:Acinar Cells / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D001943:Breast Neoplasms / Q000503:physiopathology*; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002469:Cell Separation; D003094:Collagen; D004926:Escherichia coli; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D042361:Mammary Glands, Human / Q000166:cytology*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence
chemical_list: D003094:Collagen
keywords: cancer; mechanobiology