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.mechanobiology | cancer E pithelial cells are physically coupled to their neighbors and are also in contact with the ECM. The ECM confers mechanical integrity to tissues and provides chemical, anatomical, and mechanical signals to cells, influencing differentiation, development, and pathogenesis (1-11). The extent to which mechanical cues are generated and received by individual cells has been studied both experimentally and theoretically (12)(13)(14). Progress has also been made in understanding the signaling pathways that cells use to sense external mechanics. Cell-ECM interactions are mediated in part by transmembrane proteins typified by the integrins, which link the cell's internal actin cytoskeleton with extracellular collagen fibers (15). Cells use multiple approaches for integrating mechanical cues with biochemical cues provided by soluble factors; for example, there is extensive multilayered cross-talk between integrin and TGF-β signaling (16,17). It is now also clear that key developmental regulators, such as Notch, can be directly activated by mechanical force (18,19).Less is known about the interactions of organized multicellular structures with the ECM and how those interactions affect tissue architecture, composition, and stability, as well as the molecular pathways by which these effects are mediated. In certain situations, contractile multicellular structures are able to mechanically reorganize biopolymer networks over long distances and in a highly directional manner, generating what are variously referred to as fibers, tracts, cables, straps, or lines. Regions of highly directional collagen alignment and concentration have been seen in systems ranging from single cells and tumor explants to human clinical samples (6,8,10,(20)(21)(22). Vader et al. demonstrated that the formation of long collagen lines is ...

Selective functionalization of the external surface of porous nanoparticles is of great interest for numerous potential applications in the field of nanotechnology. Regarding metal–organic frameworks (MOFs), few methods for such modifications have been reported in the literature. Herein, we focus on the covalent attachment of functional polymers on the external surface of MIL-100­(Fe) nanoparticles in order to implement properties such as increased chemical and colloidal stability or dye-labeling for the investigation of the particles by fluorescence based techniques. We prove covalent nanoparticles-polymer bond formation by liquid NMR after dissolution of the functionalized MOF under mild conditions and estimate the amount of covalently attached polymer by UV–vis spectroscopy. The functionalization of the MOF nanoparticles with fluorescently labeled polymers enables the investigation of nanoparticle uptake into tumor cells by fluorescence microscopy. Furthermore, the influence of the polymer shell on the magnetic resonance imaging activity of MIL-100­(Fe) is investigated in detail. The functionalization approach presented here is expected to enable the fabrication of hybrid nanomaterials, extending the enormous chemical space of MOFs into polymer materials.

We report on a one-step assembly route where supported lipid bilayers (SLB) are deposited on functionalized colloidal mesoporous silica (CMS) nanoparticles, resulting in a core-shell hybrid system (SLB@CMS). The supported membrane acts as an intact barrier against the escape of encapsulated dye molecules. These stable SLB@CMS particles loaded with the anticancer drug colchicine are readily taken up by cells and lead to the depolymerization of microtubules with remarkably enhanced efficiency as compared to the same dose of drug in solution.

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