The metastatic spread of cancer cells to distant sites represents the major cause of cancer-related deaths in breast cancer patients, and lungs are one of the most common sites for metastatic colonization. Developing a physiologically relevant tissue culture model to mimic lung colonization of breast cancer is crucial to the investigation of the biology of cancer metastasis and evaluation of drug treatment efficacy. Here, we described an ex vivo lung colonization assay for breast cancer using the native three-dimensional (3D) lung extracellular matrix. The native matrix was isolated from murine lung with a decellularization technique, and the preservation of extracellular matrix (ECM) composition, integrity and mechanical properties was confirmed. We showed that metastatic MDA-MB 231 and 4T1 cells invaded and colonized in the decellularized lung matrix, whereas only a small mass of non-metastatic MCF7 cells survived in the same condition. Furthermore, knockdown of ZEB1, an epithelial-mesenchymal transition (EMT) inducer, significantly reduced invasion and colonization of MDA-MB 231 cells in the decellularized lung, suggesting an important role of EMT in breast cancer metastasis. We conclude that the decellularized lung retains biophysical and biochemical properties of lung ECM and provides a powerful tool to investigate lung colonization of breast cancer.
Microscale sensors and transducers based on magnetic forces can be used to provide wireless, contamination-free interaction with micro- and nanoenvironments. However, integration of magnetic components with typical microfabrication processes can be challenging. Here we show the creation and characterization of polymer micromagnets that can be utilized in microelectromechanical systems (MEMS), microfluidics, microassembly and microrobotics applications. These magnets can be patterned using standard UV lithography, are inexpensive to manufacture, and require limited equipment to produce. We demonstrate the creation of polymer micromagnets with 3 µm feature resolution and greater than 10:1 aspect ratio, the controlled movement of freestanding structures using contact-free applied magnetic fields, and the fabrication of novel ‘hybrid’ magnetic microstructures with controlled heterogeneity of magnetic properties.
The measurement of biological events
on the surface of live cells
at the single-molecule level is complicated by several factors including
high protein densities that are incompatible with single-molecule
imaging, cellular autofluorescence, and protein mobility on the cell
surface. Here, we fabricated a device composed of an array of nanoscale
apertures coupled with a microfluidic delivery system to quantify
single-ligand interactions with proteins on the cell surface. We cultured
live cells directly on the device and isolated individual epidermal
growth factor receptors (EGFRs) in the apertures while delivering
fluorescently labeled epidermal growth factor. We observed single
ligands binding to EGFRs, allowing us to quantify the ligand turnover
in real time. These results demonstrate that this nanoaperture-coupled
microfluidic device allows for the spatial isolation of individual
membrane proteins while maintaining them in their cellular environment,
providing the capability to monitor single-ligand binding events while
maintaining receptors in their physiological environment. These methods
should be applicable to a wide range of membrane proteins.
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