Insights into the mechanobiology of cancer metastasis via microfluidic technologies.

During cancer metastasis, cancer cells will encounter various microenvironments with diverse physical characteristics. Changes in these physical characteristics such as tension, stiffness, viscosity, compression, and fluid shear can generate biomechanical cues that affect cancer cells, dynamically influencing numerous pathophysiological mechanisms. For example, a dense extracellular matrix drives cancer cells to reorganize their cytoskeleton structures, facilitating confined migration, while this dense and restricted space also acts as a physical barrier that potentially results in nuclear rupture. Identifying these pathophysiological processes and understanding their underlying mechanobiological mechanisms can aid in the development of more effective therapeutics targeted to cancer metastasis. In this review, we outline the advances of engineering microfluidic devices in vitro and their role in replicating tumor microenvironment to mimic in vivo settings. We highlight the potential cellular mechanisms that mediate their ability to adapt to different microenvironments. Meanwhile, we also discuss some important mechanical cues that still remain challenging to replicate in current microfluidic devices in future direction. While much remains to be explored about cancer mechanobiology, we believe the developments of microfluidic devices will reveal how these physical cues impact the behaviors of cancer cells. It will be crucial in the understanding of cancer metastasis, and potentially contributing to better drug development and cancer therapy.

Deleterious Mechanical Deformation Selects Mechanoresilient Cancer Cells with Enhanced Proliferation and Chemoresistance.

Cancer cells in secondary tumors are found to form metastases more efficiently as compared to their primary tumor counterparts. This is partially due to the unfavorable microenvironments encountered by metastasizing cancer cells that result in the survival of a more metastatic phenotype from the original population. However, the role of deleterious mechanical stresses in this change of metastatic potential is unclear. Here, by forcing cancer cells to flow through small capillary-sized constrictions, it is demonstrated that mechanical deformation can select a tumor cell subpopulation that exhibits resilience to mechanical squeezing-induced cell death. Transcriptomic profiling reveals up-regulated proliferation and DNA damage response pathways in this subpopulation, which are further translated into a more proliferative and chemotherapy-resistant phenotype. These results highlight a potential link between the microenvironmental physical stresses and the enhanced malignancy of metastasizing cancer cells which may be utilized as a therapeutic strategy in preventing the metastatic spread of cancer cells.

Engineering confining microenvironment for studying cancer metastasis.

The physical microenvironment of cells plays a fundamental role in regulating cellular behavior and cell fate, especially in the context of cancer metastasis. For example, capillary deformation can destroy arrested circulating tumor cells while the dense extracellular matrix can form a physical barrier for invading cancer cells. Understanding how metastatic cancer cells overcome the challenges brought forth by physical confinement can help in developing better therapeutics that can put a stop to this migratory stage of the metastatic cascade. Numerous in vivo and in vitro assays have been developed to recapitulate the metastatic processes and study cancer cell migration in a confining microenvironment. In this review, we summarize some of the representative techniques and the exciting new findings. We critically review the advantages, as well as challenges associated with these tools and methodologies, and provide a guide on the applications that they are most suited for. We hope future efforts that push forward our current understanding on metastasis under confinement can lead to novel and more effective diagnostic and therapeutic strategies against this dreaded disease.

Preparation and application of ratiometric polystyrene-based microspheres as oxygen sensors.

Mono-dispersed polystyrene-based microspheres with diameters about 1 µm encapsulating rhodamine moieties as oxygen insensitive internal reference probes and platinum octaethylporphyrin units as oxygen sensitive probes were synthesized as new ratiometric oxygen sensors (Rhod-PtOEP-PS). The dual luminophors of rhodamines and platinum porphyrin moieties exhibited emissions maxima at 585 nm and 644 nm, respectively. The microspheres showed good oxygen sensing properties in different oxygen partial pressures (pO2) and dissolved oxygen (DO) concentrations. It was found the oxygen probes and reference probes in microspheres showed higher photo-stability than their corresponding free fluorophores in solution. The microspheres also showed good sensitivity for air-pressure and cellular oxygen in cell culture medium. These microspheres were used to detect DOs in a few kinds of liquids including some daily drinks and it was found the measured errors were within positive/negative 11% as compared with the measured results using traditional oxygen electrodes.

Silver Nanowire-Induced Sensitivity Enhancement of Optical Oxygen Sensors Based on AgNWs-Palladium Octaethylporphine-Poly(methyl methacrylate) Microfiber Mats Prepared by Electrospinning.

Sensitivity enhancement of optical oxygen sensors is crucial for the characterization of nearly anoxic systems and oxygen quantification in trace amounts. In this work, for the first time we presented the introduction of silver nanowires (AgNWs) as a sensitivity booster for optical oxygen sensors based on AgNWs-palladium octaethylporphine-poly(methyl methacrylate) (AgNWs@PdOEP-PMMA) microfiber mats prepared by electrospinning. Herein, a series of sensing microfiber mats with different loading ratios of high aspect ratio AgNWs were fabricated, and the corresponding sensitivity enhancement was systematically investigated. With increasing incorporated ratios, the AgNWs@PdOEP-PMMA-sensing microfiber mats exhibited a swift response (approx. 1.8 s) and a dramatic sensitivity enhancement (by 243% for the range of oxygen concentration 0-10% and 235% for the range of oxygen concentration 0-100%) when compared to the pure PdOEP-PMMA microfiber mat. Additionally, the as-prepared sensing films were experimentally confirmed to be highly photostable and reproducible. The advantages of AgNW-induced sensitivity enhancement could be useful for the rational design and realization of revolutionary highly sensitive sensors and expected to be readily applicable to many other high-performance gas sensor devices.