title: Non-invasive single-cell biomechanical analysis using live-imaging datasets.
abstract: The physiological state of a cell is governed by a multitude of processes and can be described by a combination of mechanical, spatial and temporal properties. Quantifying cell dynamics at multiple scales is essential for comprehensive studies of cellular function, and remains a challenge for traditional end-point assays. We introduce an efficient, non-invasive computational tool that takes time-lapse images as input to automatically detect, segment and analyze unlabeled live cells; the program then outputs kinematic cellular shape and migration parameters, while simultaneously measuring cellular stiffness and viscosity. We demonstrate the capabilities of the program by testing it on human mesenchymal stem cells (huMSCs) induced to differentiate towards the osteoblastic (huOB) lineage, and T-lymphocyte cells (T cells) of naïve and stimulated phenotypes. The program detected relative cellular stiffness differences in huMSCs and huOBs that were comparable to those obtained with studies that utilize atomic force microscopy; it further distinguished naïve from stimulated T cells, based on characteristics necessary to invoke an immune response. In summary, we introduce an integrated tool to decipher spatiotemporal and intracellular dynamics of cells, providing a new and alternative approach for cell characterization.
authors.affiliation: Department of Applied Mathematics and Sciences, Khalifa University, P.O. Box 127788, Abu Dhabi, UAE.
authors.forename: Yanthe E
authors.identifier: 0000-0002-5662-1389
authors.initials: YE
authors.lastname: Pearson
authors.affiliation: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Amanda W
authors.initials: AW
authors.lastname: Lund
authors.affiliation: Endothelix, Inc., 2500 West Loop, South Houston, TX 77027, USA.
authors.forename: Alex W H
authors.identifier: 0000-0002-2053-5139
authors.initials: AW
authors.lastname: Lin
authors.affiliation: Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore 138602 Mimetas BV, JH Oortweg 19, Leiden 2333 CH, The Netherlands.
authors.forename: Chee P
authors.identifier: 0000-0002-4508-2770
authors.initials: CP
authors.lastname: Ng
authors.affiliation: Department of Biomedical Engineering, Khalifa University, P.O. Box 127788, Abu Dhabi, UAE.
authors.forename: Aysha
authors.initials: A
authors.lastname: Alsuwaidi
authors.affiliation: Department of Biomedical Engineering, Khalifa University, P.O. Box 127788, Abu Dhabi, UAE.
authors.forename: Sara
authors.identifier: 0000-0001-9586-1214
authors.initials: S
authors.lastname: Azzeh
authors.affiliation: Department of Applied Mathematics and Sciences, Khalifa University, P.O. Box 127788, Abu Dhabi, UAE.
authors.forename: Deborah L
authors.identifier: 0000-0001-5353-8179
authors.initials: DL
authors.lastname: Gater
authors.affiliation: Department of Biomedical Engineering, Khalifa University, P.O. Box 127788, Abu Dhabi, UAE jeremy.teo@kustar.ac.ae.
authors.forename: Jeremy C M
authors.identifier: 0000-0001-6869-3833
authors.initials: JC
authors.lastname: Teo
mesh_terms: D000328:Adult; D000465:Algorithms; D000818:Animals; D001331:Automation; D001696:Biomechanical Phenomena / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019992:Databases as Topic; D004548:Elasticity; D006801:Humans; D021621:Imaging, Three-Dimensional; D015759:Ionomycin / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010641:Phenotype; D059010:Single-Cell Analysis / Q000379:methods*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014783:Viscosity
chemical_list: D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate
keywords: Cell biomechanics; Cell migration; Live imaging; Mechanobiology; Mesenchymal stem cells; T-lymphocyte cells