High‐Throughput Cellular Heterogeneity Analysis in Cell Migration at the Single‐Cell Level

Cancer cell migration represents an essential step toward metastasis and cancer deaths. However, conventional drug discovery focuses on cytotoxic and growth‐inhibiting compounds rather than inhibitors of migration. Drug screening assays generally measure the average response of many cells, masking d...

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Bibliographic Details
Published inSmall (Weinheim an der Bergstrasse, Germany) Vol. 19; no. 6; pp. e2206754 - n/a
Main Authors Zhou, Mengli, Ma, Yushu, Chiang, Chun‐Cheng, Rock, Edwin C., Luker, Kathryn E., Luker, Gary D., Chen, Yu‐Chih
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 01.02.2023
Subjects
breast cancer
Cancer
Cell adhesion & migration
Cell Line, Tumor
cell migration
Cell Movement
Computer vision
Drug Discovery
Heterogeneity
High-Throughput Screening Assays
image processing
Metastasis
Microfluidics
Nanotechnology
Single-Cell Analysis
image processing
cell migration
breast cancer
metastasis
microfluidics
single-cell analysis
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Summary:Cancer cell migration represents an essential step toward metastasis and cancer deaths. However, conventional drug discovery focuses on cytotoxic and growth‐inhibiting compounds rather than inhibitors of migration. Drug screening assays generally measure the average response of many cells, masking distinct cell populations that drive metastasis and resist treatments. Here, this work presents a high‐throughput microfluidic cell migration platform that coordinates robotic liquid handling and computer vision for rapidly quantifying individual cellular motility. Using this innovative technology, 172 compounds were tested and a surprisingly low correlation between migration and growth inhibition was found. Notably, many compounds were found to inhibit migration of most cells while leaving fast‐moving subpopulations unaffected. This work further pinpoints synergistic drug combinations, including Bortezomib and Danirixin, to stop fast‐moving cells. To explain the observed cell behaviors, single‐cell morphological and molecular analysis were performed. These studies establish a novel technology to identify promising migration inhibitors for cancer treatment and relevant applications. This work presents a high‐throughput single‐cell migration platform that coordinates robotic liquid handling and autonomous image processing for quantifying cellular heterogeneity and dynamics in migration. Using this innovative technology, this work has revealed a surprisingly low correlation between inhibition of cell migration and growth, and many compounds inhibited migration of most cells but not fast‐moving subpopulations.
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M.Z. and Y.-C.C. performed the fabrication of microfluidic devices. M.Z. and Y.-C.C. performed the cell migration experiments. Y.M. developed the software for image processing. C.-C.C. and Y.-C.C. performed the single-cell RNA-Seq experiments. E.C.R. and Y.-C.C. performed the sequencing read alignment and data analysis. K.E.L., G.D.L., and Y.-C.C. performed cell transfection and transduction. Y.-C.C. supervised the study. M.Z., and Y.-C.C. wrote the manuscript. All authors discussed the results and commented on the manuscript.
Author Contributions
ISSN:1613-6810
1613-6829
1613-6829
DOI:10.1002/smll.202206754