Bay Area Physical Sciences Oncology Center and Departments of Physics and Mathematics, University of California, Berkeley, CA 94720.
Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):658-63. doi: 10.1073/pnas.1311312110. Epub 2013 Dec 30.
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.
细胞和多细胞结构可以在其细胞外基质环境中机械排列和集中纤维，并通过分化、分支或解体来感知和响应机械线索。在这里，我们表明，结构完整性受损的乳腺腺泡可以通过形成长胶原线相互连接。这些胶原线然后协调并加速向侵袭表型的转变。在空间上协调的 12.5±4.7 h 内，相互作用的腺泡开始解体，而与其他腺泡没有机械相互作用的腺泡解体较慢（在 21.8±4.1 h）且程度较小（P<0.0001）。当用激光切割腺泡之间的定向机械连接时，腺泡恢复到缓慢解体的表型。当腺泡完全与其他腺泡以及通过边长<900 μm 的盒式切割与大块凝胶机械隔离时，20 次实验中的 20 次都阻止了侵袭表型的转变，无论等待时间如何。因此，一对或多对乳腺腺泡可以通过胶原基质进行长距离的机械相互作用，并且这些定向机械相互作用促进了侵袭表型的转变。
