Microfluidic Cell Sorting by Stiffness to Examine Heterogenic Responses of Cancer Cells to Chemotherapy

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2018 Feb 16

PMID 29445159

Citations 26

Authors

Muhymin Islam

Roman Mezencev

Brynn McFarland

Hannah Brink

Betsy Campbell

Bushra Tasadduq

Edmund K Waller

Wilbur Lam

Alexander Alexeev

Todd Sulchek

Affiliations

Soon will be listed here.

Abstract

Cancers consist of a heterogeneous populations of cells that may respond differently to treatment through drug-resistant sub-populations. The scarcity of these resistant sub-populations makes it challenging to understand how to counter their resistance. We report a label-free microfluidic approach to separate cancer cells treated with chemotherapy into sub-populations enriched in chemoresistant and chemosensitive cells based on the differences in cellular stiffness. The sorting approach enabled analysis of the molecular distinctions between resistant and sensitive cells. Consequently, the role of multiple mechanisms of drug resistance was identified, including decreased sensitivity to apoptosis, enhanced metabolism, and extrusion of drugs, and, for the first time, the role of estrogen receptor in drug resistance of leukemia cells. To validate these findings, several inhibitors for the identified resistance pathways were tested with chemotherapy to increase cytotoxicity sevenfold. Thus, microfluidic sorting can identify molecular mechanisms of drug resistance to examine heterogeneous responses of cancers to therapies.

Citing Articles

Characterization, Enrichment, and Computational Modeling of Cross-Linked Actin Networks in Transformed Trabecular Meshwork Cells.

Li H, Harvey D, Dai J, Swingle S, Compton A, Sugali C Invest Ophthalmol Vis Sci. 2025; 66(2):65.

PMID: 40009371 PMC: 11878246. DOI: 10.1167/iovs.66.2.65.

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Measuring Melanoma Nanomechanical Properties in Relation to Metastatic Ability and Anti-Cancer Drug Treatment Using Scanning Ion Conductance Microscopy.

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PMID: 37830615 PMC: 10571876. DOI: 10.3390/cells12192401.

Molecular mechanocytometry using tension-activated cell tagging.

Ma R, Rashid S, Velusamy A, Deal B, Chen W, Petrich B Nat Methods. 2023; 20(11):1666-1671.

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Microfluidic Isolation of Disseminated Tumor Cells from the Bone Marrow of Breast Cancer Patients.

Volmer L, Onder C, Volz B, Singh A, Brucker S, Engler T Int J Mol Sci. 2023; 24(18).

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