Microfluidics-Based Single-Cell Protrusion Analysis for Screening Drugs Targeting Subcellular Mitochondrial Trafficking in Cancer Progression.

Abstract

Cancer cell migration is often guided by cell protrusions, whose formation and activity involve subcellular localization of mitochondria. However, the role of subcellular mitochondrial trafficking during cell protrusion generation is not well-understood amidst a lack of quantitative data. Here, we present a high-throughput microfluidic platform that enables the quantitative, single-cell precision analysis of cell protrusion formation during cell migration that is regulated by subcellular mitochondrial trafficking. Gene expression profiling of the isolated cell protrusions suggested that mitochondria were found in high numbers within cell protrusions, a finding validated by mitochondrial staining. Quantitative analysis revealed that the formation of cell protrusions could be effectively suppressed by inhibiting subcellular mitochondrial trafficking. We further demonstrated that rapid screening of mitochondria-specific therapeutic drugs to evaluate their effects on cell protrusion formation with single-cell precision could be achieved in the microfluidic platform, which could have clinical utility in the development of new anticancer agents.