Journal
ACS SENSORS
Volume 6, Issue 8, Pages 2838-2844Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acssensors.1c01037
Keywords
cell adhesion strength; single cell; mechanical phenotype characterization; long-channel constriction-based microfluidics; cell transit velocity; friction coefficient
Funding
- National Natural Science Foundation of China [61673195]
- Natural Science Research of Jiangsu Higher Education Institutions of China (CN) [18KJB510008]
- Priority Academic Program Development of Jiangsu Higher Education Institutions [PAPD2018-87]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX20_3029]
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This study introduces a novel method for high-throughput evaluation of cancer cell adhesion strength in long-channel constriction based on friction coefficient. By simplifying the linear elasticity of compressed cells, the influence of cell size heterogeneity is effectively mitigated in determining adhesion strength.
The adhesion strength of a cancer cell is a valuable biophysical marker of its metastatic potential, tightly associated with various metastatic processes; for example, cancer cells escape from a primary tumor, and circulating tumor cells (CTCs) are anchored to the vessel wall. Although constriction-based microfluidics can realize the high-throughput characterization of single-cell deformability, due to the influence of cell size heterogeneity, accurately evaluating the adhesion strength of a cancer cell at high throughputs in constriction remains difficult. In this paper, we first proposed an approach for the assessment of adhesion strength of BGC-823 and SGC-7901 cell lines at high throughputs based on a friction coefficient using the constant velocity stage of cell transit in a long-channel constriction. Cell size was proven to be independent of adhesion strength by cell detachment assay; however, it has large effects on cell transit velocity in constriction. Therefore, the linear elasticity of a completely deformed cell in constriction is simplified as a compressed spring model, effectively reducing the influence of cell size heterogeneity. Theoretically, our proposed model can well offset the influence of cell size by cell transit velocity, while our experimental results indicate that the friction coefficient has a good linear relationship with the logarithm of the adhesion strength too. Therefore, our proposed approach can realize accurate characterization of cell adhesion strength at high throughputs using long-channel constriction-based microfluidics. Hence, this work might enrich the functions of constriction-based microfluidics and bring new insights into the characterization of mechanical phenotypes.
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