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Molecular recognition toward specific cells is a key issue for effective disease, such as cancer, diagnosis and therapy. Although many molecular probes such as aptamers and antibodies can recognize the unique molecular signatures of cancer cells, some of these probes only have relatively weak binding affinities. This results in poor signaling and hinders cell targeting. Here, we use Au-Ag nanorods (NRs) as a nanoplatform for multivalent binding by multiple aptamers on the rod to increase both the signal and binding strengths of these aptamers in cancer cell recognition. Up to 80 fluorophore-labeled aptamers can be attached on a 12 nm x 56 nm NR, resulting in a much stronger fluorescence signal than that of an individual dye-labeled aptamer probe. The molecular assembly of aptamers on the NR surfaces also significantly improves the binding affinity with cancer cells through simultaneous multivalent interactions with the cell membrane receptors. This leads to an affinity at least 26-fold higher than the intrinsic affinity of the original aptamer probes. As determined by flow cytometric measurements, an enhancement in fluorescence signal in excess of 300fold is obtained for the NR-aptamer-labeled cells compared with those labeled by individual aptamer probes. Therefore, the molecular assembly of aptamers clearly shows potential applications for the elucidation of cells with low density of binding sites, or with relatively weak binding probes, and can thus greatly improve our ability to perform cellular imaging and targeting. This is an excellent example of using nanomaterials to develop advanced molecular binders with greatly improved properties for cellular studies.

As cancer cells traverse collagen-rich extracellular matrix (ECM) barriers and intravasate, they adopt a fibroblast-like phenotype and engage undefined proteolytic cascades that mediate invasive activity. Herein, we find that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM. Using fibroblasts isolated from gene-targeted mice, a matrix metalloproteinase (MMP)--dependent activity is identified that drives invasion independently of plasminogen, the gelatinase A/TIMP-2 axis, gelatinase B, collagenase-3, collagenase-2, or stromelysin-1. In contrast, deleting or suppressing expression of the membrane-tethered MMP, MT1-MMP, in fibroblasts or tumor cells results in a loss of collagenolytic and invasive activity in vitro or in vivo. Thus, MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity.

Author(s): Nicole Vincent Jordan [1]; Aditya Bardia [1, 2]; Ben S. Wittner [1, 2]; Cyril Benes [1, 2]; Matteo Ligorio [1, 3]; Yu Zheng [1]; Min Yu [1]; Tilak K. [...]

An automated analysis system for the rapid measurement of dielectrophoretic collection spectra of mammalian cells is described. Cells are injected onto an electrode configuration having regions with different electric field gradients, and cell movement to or from these regions is determined by computerized image analysis as a function of the applied electric field frequency. Data are presented to show that cultured murine erythroleukemia cells undergo a significant alteration in their dielectrophoretic collection spectrum following treatment with hexamethylene bisacetamide or dimethylsulfoxide, agents that induce terminal differentiation in these otherwise malignant cells. These changes appear to arise from characteristic alterations in membrane capacitance and conductance as the cells differentiate.