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Size-based sorting of cancer cells reveals functional heterogeneity among subpopulations

Yilmaz, Esra LU orcid ; Fan, Zhimeng LU ; Beech, Jason P. LU ; Swaminathan, Vinay S. LU orcid and Tegenfeldt, Jonas O. LU orcid (2026) In Lab on a Chip 26(11). p.3459-3472
Abstract

Cancer cells display marked heterogeneity in size and morphology, traits long recognized in pathology as indicators of pleomorphism and poor prognosis. Yet, the functional significance and phenotypic consequences of these morphological variations within a single cancer cell population remain poorly understood. Here, we employed a deterministic lateral displacement (DLD) microfluidic device with a circular micro-pillar array to fractionate MDA-MB-231 breast cancer cells into distinct small and large subpopulations based on size. Following sorting, the isolated fractions were expanded in culture and subjected to assays to measure proliferation, migration and invasion. We found that these subpopulations maintained their characteristic... (More)

Cancer cells display marked heterogeneity in size and morphology, traits long recognized in pathology as indicators of pleomorphism and poor prognosis. Yet, the functional significance and phenotypic consequences of these morphological variations within a single cancer cell population remain poorly understood. Here, we employed a deterministic lateral displacement (DLD) microfluidic device with a circular micro-pillar array to fractionate MDA-MB-231 breast cancer cells into distinct small and large subpopulations based on size. Following sorting, the isolated fractions were expanded in culture and subjected to assays to measure proliferation, migration and invasion. We found that these subpopulations maintained their characteristic sizes over several days and exhibited distinct functional behaviors that differentially contributed to the overall invasive phenotype of MDA-MB-231 cells. Notably, while the two subpopulations proliferated at the same rate, the small-cell fraction displayed enhanced migratory capacity and invasion both in 2D and 3D assays, thus representing the primary drivers of the invasive phenotype of MDA-MB-231 cells. Together, our findings demonstrate that label-free, size-based sorting reveals biologically meaningful functional heterogeneity within morphologically diverse cancer cell populations.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microfluidics
in
Lab on a Chip
volume
26
issue
11
pages
14 pages
publisher
Royal Society of Chemistry
external identifiers
  • pmid:42083795
  • scopus:105037514265
ISSN
1473-0197
DOI
10.1039/d5lc01042j
language
English
LU publication?
yes
additional info
Publisher Copyright: This journal is © The Royal Society of Chemistry, 2026.
id
12e3d4db-d5b9-4306-9b30-a9a431afa22c
date added to LUP
2026-06-21 16:51:57
date last changed
2026-07-06 23:50:03
@article{12e3d4db-d5b9-4306-9b30-a9a431afa22c,
  abstract     = {{<p>Cancer cells display marked heterogeneity in size and morphology, traits long recognized in pathology as indicators of pleomorphism and poor prognosis. Yet, the functional significance and phenotypic consequences of these morphological variations within a single cancer cell population remain poorly understood. Here, we employed a deterministic lateral displacement (DLD) microfluidic device with a circular micro-pillar array to fractionate MDA-MB-231 breast cancer cells into distinct small and large subpopulations based on size. Following sorting, the isolated fractions were expanded in culture and subjected to assays to measure proliferation, migration and invasion. We found that these subpopulations maintained their characteristic sizes over several days and exhibited distinct functional behaviors that differentially contributed to the overall invasive phenotype of MDA-MB-231 cells. Notably, while the two subpopulations proliferated at the same rate, the small-cell fraction displayed enhanced migratory capacity and invasion both in 2D and 3D assays, thus representing the primary drivers of the invasive phenotype of MDA-MB-231 cells. Together, our findings demonstrate that label-free, size-based sorting reveals biologically meaningful functional heterogeneity within morphologically diverse cancer cell populations.</p>}},
  author       = {{Yilmaz, Esra and Fan, Zhimeng and Beech, Jason P. and Swaminathan, Vinay S. and Tegenfeldt, Jonas O.}},
  issn         = {{1473-0197}},
  keywords     = {{microfluidics}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{11}},
  pages        = {{3459--3472}},
  publisher    = {{Royal Society of Chemistry}},
  series       = {{Lab on a Chip}},
  title        = {{Size-based sorting of cancer cells reveals functional heterogeneity among subpopulations}},
  url          = {{http://dx.doi.org/10.1039/d5lc01042j}},
  doi          = {{10.1039/d5lc01042j}},
  volume       = {{26}},
  year         = {{2026}},
}