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

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.