Two of the classical hallmarks of cancer are uncontrolled cell division and tissue invasion, which turn the disease into a systemic, life-threatening condition. Although both processes are studied, a clear correlation between cell division and motility of cancer cells has not been described previously. Here, we experimentally characterize the dynamics of invasive and non-invasive breast cancer tissues using human and murine model systems. The intrinsic tissue velocities, as well as the divergence and vorticity around a dividing cell correlate strongly with the invasive potential of the tissue, thus showing a distinct correlation between tissue dynamics and aggressiveness. We formulate a model which treats the tissue as a visco-elastic continuum. This model provides a valid reproduction of the cancerous tissue dynamics, thus, biological signaling is not needed to explain the observed tissue dynamics. The model returns the characteristic force exerted by an invading cell and reveals a strong correlation between force and invasiveness of breast cancer cells, thus pinpointing the importance of mechanics for cancer invasion.

Novel RNA-based technologies provide an avenue of possibilities to control the regulation of gene expression in cells. To realize the full potential of small interfering RNA (siRNA)-based therapy, efficient delivery vehicles and novel strategies for triggering release from carrier vehicles have to be developed. Gold nanoparticles (AuNPs) with sizes of ∼50–150 nm have the ability to accumulate in tumor tissue and can be transported across the membrane by endocytosis. Therefore, a laser-controlled oligonucleotide release from such particles is of particular interest. Here, we quantify the loading of specifically attached microRNA oligonucleotides (miRNA) onto single gold nanoparticles with diameters of 80, 100, 150, and 200 nm. We show that AuNPs have a curvature-dependent density of miRNA loading: the higher the curvature, the higher the loading density. Moreover, we demonstrate how one sensing strand of an RNA duplex can be dehybridized and hence released from the AuNP by heating the AuNP by irradiation with a near-infrared (NIR) laser. Laser-induced release is also demonstrated inside living cells. Together, these findings show that plasmonic nanoparticles with high curvatures are ideal carriers of oligonucleotides into cells, and their cargo can be released in a controlled manner by a thermoplasmonic mechanism. Importantly, this remotely controlled release strategy can be applied to any cargo attached to a plasmonic nanocarrier, on either the single particle or ensemble level.

mechanical interplays between cancer cells and the extracellular matrix trigger adhesion-mediated signaling pathways that affect not only the cells' mechanical properties such as motility and rigidity but also the cell's viability such as proliferation and apoptosis. In this study, we interrogated whether the anti-cancer drug resistance of breast cancer cells can be discerned by monitoring the proliferation of breast cancer cells seeded on nanoscaffolds. The nanoscaffolds help systematically control the maturation of focal adhesions on well-defined nano-sized areas and distances. They were fabricated as two-dimensional arrays of gold nanoislands on glass substrates using our bottom-up procedures combining nanosphere lithography and orthogonal chemistry. By varying the size of nanospheres (300-1,000 nm) used for nanolithography, the size and spacing of nanoislands were controlled. The MCF-7 and MCF-7/ADR cells were investigated as the drug-sensitive and the drugresistant breast cancer cell lines, respectively. The difference in the doxorubicin-sensitivity of the two cell lines was confirmed by the MTT assay. The cell proliferation was determined from the phase contrast images taken every 24 hours after the initial cell seeding on the nanoscaffolds. We found that the proliferation of the drug-sensitive breast cancer cells was highly affected by the geometrical characteristics of the underlying nanoscaffolds. Unlike the MCF-7 cells, the proliferation of the drug-resistant breast cancer cells was not noticeably affected by the nanoscaffolds for the first two days of observation. We postulate that MCF-7/ADR cells showed the abnormal maturation of focal adhesions beyond the restricted area and thus continuously proliferated. We also observed a faster wound closure for MCR-7/ADR cells than MCF-7 cells. The increase in 2D motility of MCF-7/ADR could be resulted from higher levels of the traction force generated by the enhanced focal adhesions. In conclusion, we found that the abnormal maturation of focal adhesions via vinculin overexpression caused the uncontrolled proliferation and resulted in the acquisition of the drug resistance in breast cancer cells. We suggest that the restoration of the normal maturation of focal adhesions might be a promising way to sensitize the anti-cancer drug response from breast cancer cells.

No abstract