We employed direct-current electric fields (dcEFs) to modulate the chemotaxis of lung cancer cells in a microfluidic cell culture device that incorporates both stable concentration gradients and dcEFs. We found that the chemotaxis induced by a 0.5 lM/mm concentration gradient of epidermal growth factor can be nearly compensated by a 360 mV/mm dcEF. When the effect of chemical stimulation was balanced by the electrical drive, the cells migrated randomly, and the path lengths were largely reduced. We also demonstrated electrically modulated chemotaxis of two types of lung cancer cells with opposite directions of electrotaxis in this device. V C 2014 AIP Publishing LLC. [http://dx

BackgroundCell membranes exhibit abundant types of responses to external stimulations. Intuitively, membrane topography should be sensitive to changes of physical or chemical factors in the microenvironment. We employed the non-interferometric wide-field optical profilometry (NIWOP) technique to quantify the membrane roughness of living neuroblastoma cells under various treatments that could change the mechanical properties of the cells.ResultsThe membrane roughness was reduced as the neuroblastoma cell was treated with paclitaxel, which increases cellular stiffness by translocating microtubules toward the cell membranes. The treatment of positively charged gold nanoparticles (AuNPs) showed a similar effect. In contrast, the negatively charged AuNPs did not cause significant changes of the membrane roughness. We also checked the membrane roughness of fixed cells by using scanning electron microscopy (SEM) and confirmed that the membrane roughness could be regarded as a parameter reflecting cellular mechanical properties. Finally, we monitored the temporal variations of the membrane roughness under the treatment with a hypertonic solution (75 mM sucrose in the culture medium). The membrane roughness was increased within 1 h but returned to the original level after 2 h.ConclusionsThe results in the present study suggest that the optical measurement on membrane roughness can be regarded as a label-free method to monitor the changes in cell mechanical properties or binding properties of nanoparticles on cell surface. Because the cells were left untouched during the measurement, further tests about cell viability or drug efficacy can be done on the same specimen. Membrane roughness could thus provide a quick screening for new chemical or physical treatments on neuronal cells.

Using a cell culture chip with a deformable substrate driven by a hydraulic force, we investigated the motility of cancer cells affected by myofibroblasts undergoing cyclic tensile strain (CTS). CTS reduced both the expression of α-smooth muscle actin in the myofibroblast and the ability of the myofibroblast to accelerate cancer cell migration. However, with the treatment of a pro-inflammatory factor interleukin-1β on the myofibroblasts, the effects of CTS on the myofibroblast were diminished. This result suggests an antagonism between mechanical and chemical stimulations on mediating cancer metastasis by the stromal myofibroblast.

Abstract:We used a spatial light modulator to project an optical micropattern of 473 nm light with a quartic intensity gradient on a single lung cancer cell. We observed that the intracellular amounts of reactive oxygen species (ROS) of the cancer cells were proportional to the intensity of the blue light, and the blue light intensity gradients could drive directional cell migration. This optically induced directional cell migration was inhibited by a ROS scavenger in the culture medium in a dosedependent manner. In contrast, the ROS levels in fibroblasts were saturated by the blue light at low intensity and therefore the fibroblasts did not exhibit directional migration in the intensity gradient.

Abstract. The membrane roughness of Neuro-2a neroblastoma cells is measured by using noninterferometric widefield optical profilometry. The cells are treated with the fibril and oligomer conformers of amyloid-beta (Aβ) 42, which is a peptide of 42 amino acids related to the development of Alzheimer's disease. We find that both the Aβ42 fibrils and Aβ42 oligomers reduced the cell membrane roughness, but the effect of Aβ42 oligomers was faster and stronger than that of the fibrils. We also apply direct-current electric field (dcEF) stimulations on the cells. A dcEF of 300 mV∕mm can increase the membrane roughness under the treatment of Aβ42. These results suggest that Aβ42 can decrease the membrane compliance of live neuroblastoma cells, and dcEFs may counteract this effect. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

We investigated the effects of cigarette smoke extract (CSE) on lung fibroblasts and found that the invasiveness of lung cancer cells was facilitated by the conditioned medium from CSE‐treated fibroblasts. CSE induced autophagy in fibroblasts and increased the expression of autophagy‐related proteins, including optineurin and Ras‐related protein Rab1B. Afterward, the fibroblasts produced high levels of interleukin‐8 (IL‐8), which promoted cancer cell invasion. The inhibition of either optineurin or Rab1B abrogated a rise in microtubule‐associated protein 1 light chain 3 β and a decrease in p62 protein, as well as the production of IL‐8, in CSE‐treated fibroblasts. A three‐dimensional invasion assay using cancer cell spheroids revealed that the invasion of cancer cells alone and the fibroblast‐led cancer cell invasion were both enhanced by the conditioned media from CSE‐treated fibroblasts. These results suggest that cigarette smoke may induce autophagy and IL‐8 secretion in lung fibroblasts and modify the microenvironment to favor invasion of lung cancer cells.

We used a liquid-crystal spatial light modulator to project 473 nm light patterns surrounding a region of adherent cells and achieved an arbitrarily micropatterned cell culture. For a group of ∼60 cells, the cell boundaries fit the pattern of light within 15% deviation of the side length. We also demonstrated a wound-healing experiment with a definite starting temporal point by using this technique. While observing mitochondrial structures in the illuminated cells, we found that the 473 nm light damaged the integrity of mitochondria and thus prohibited cell proliferation in the illuminated region.

Background Tunneling nanotubes (TNTs) are special membrane structures for intercellular communications. Vital cargoes (such as mitochondria) could be delivered from healthy cells to rescue damaged ones through TNTs. The TNTs could be utilized for the purpose of systematic delivery of therapeutic agents between cells. However, there are insufficient studies on the controlled enhancement of TNT formations. The purpose of this study is to understand how macrophages influence the TNT formation in cancer cells. Results Here we compared the capabilities of inducing TNTs in human pancreatic cancer cells (PANC-1) of the media conditioned by M0, M1 and M2 macrophages derived from THP-1 cells. The M0 and M1 macrophage conditioned media promoted TNT formation. Using a focused ion beam to cut through a TNT, we observed tunnel-like structures inside dense cytoskeletons with scanning electron microscopy. The TNT formation correlated with raised motility, invasion, and epithelial–mesenchymal transition in the PANC-1 cells. Mitochondria and lysosomes were also found to be transported in the TNTs. Conclusions These results suggest that TNT formation could be one of the responses to the immune stress in pancreatic cancer cells caused by M0 and M1 macrophages. This finding is valuable for the development of macrophage-targeting cancer therapy.