Characterizing cellular mechanical phenotypes with mechano-node-pore sensing

• Published in: Microsystems & nanoengineering 2018-03, Vol.4 (1), p.17091, Article 17091
• Main Authors: Kim, Junghyun, Han, Sewoon, Lei, Andy, Miyano, Masaru, Bloom, Jessica, Srivastava, Vasudha, Stampfer, Martha R., Gartner, Zev J., LaBarge, Mark A., Sohn, Lydia L.
• Format: Article
• Language: English
• Subjects: 639/166; 639/925/350/877; BASIC BIOLOGICAL SCIENCES; Biomarkers; biosensors; Biotechnology; Cell lines; Cytometry; Cytoskeleton; Deformability; Deformation; Deformation resistance; Engineering; Epithelial cells; Flow cytometry; Formability; Genetic transformation; Instruments & Instrumentation; label-free; Mammary gland; mechanical phenotyping; Mechanical properties; Microfluidics; node-pore sensing; Recovery time; Science & Technology - Other Topics; Strain
• ISSN: 2055-7434; 2096-1030; 2055-7434
• DOI: 10.1038/micronano.2017.91

The mechanical properties of cells change with their differentiation, chronological age, and malignant progression. Consequently, these properties may be useful label-free biomarkers of various functional or clinically relevant cell states. Here, we demonstrate mechano-node-pore sensing (mechano-NPS), a multi-parametric single-cell-analysis method that utilizes a four-terminal measurement of the current across a microfluidic channel to quantify simultaneously cell diameter, resistance to compressive deformation, transverse deformation under constant strain, and recovery time after deformation. We define a new parameter, the whole-cell deformability index (wCDI), which provides a quantitative mechanical metric of the resistance to compressive deformation that can be used to discriminate among different cell types. The wCDI and the transverse deformation under constant strain show malignant MCF-7 and A549 cell lines are mechanically distinct from non-malignant, MCF-10A and BEAS-2B cell lines, and distinguishes between cells treated or untreated with cytoskeleton-perturbing small molecules. We categorize cell recovery time, Δ T r , as instantaneous (Δ T r ~0 ms), transient (Δ T r ⩽40 ms), or prolonged (Δ T r >40 ms), and show that the composition of recovery types, which is a consequence of changes in cytoskeletal organization, correlates with cellular transformation. Through the wCDI and cell-recovery time, mechano-NPS discriminates between sub-lineages of normal primary human mammary epithelial cells with accuracy comparable to flow cytometry, but without antibody labeling. Mechano-NPS identifies mechanical phenotypes that distinguishes lineage, chronological age, and stage of malignant progression in human epithelial cells. Sensors: Microfluidic-based cell measurements could aid clinical diagnosis A simple and innovative technique for measuring the mechanical properties of cells could lead to a versatile clinical diagnostic tool. The ability to measure differences in the mechanical properties of cells can be used to detect changes in cells that are caused by disease, aging, or environmental interactions. Present technologies for performing such measurements, however, can analyse only a few cells each hour. This led Lydia Sohn at the University of California, Berkeley, in the United States, and colleagues to use a microfluidic platform that integrates node-pore sensors with a contraction channel to measure mechanical differences in populations of cells effi