title: Microconstriction arrays for high-throughput quantitative measurements of cell mechanical properties.
abstract: We describe a method for quantifying the mechanical properties of cells in suspension with a microfluidic device consisting of a parallel array of micron-sized constrictions. Using a high-speed charge-coupled device camera, we measure the flow speed, cell deformation, and entry time into the constrictions of several hundred cells per minute during their passage through the device. From the flow speed and the occupation state of the microconstriction array with cells, the driving pressure across each constriction is continuously computed. Cell entry times into microconstrictions decrease with increased driving pressure and decreased cell size according to a power law. From this power-law relationship, the cell elasticity and fluidity can be estimated. When cells are treated with drugs that depolymerize or stabilize the cytoskeleton or the nucleus, elasticity and fluidity data from all treatments collapse onto a master curve. Power-law rheology and collapse onto a master curve are predicted by the theory of soft glassy materials and have been previously shown to describe the mechanical behavior of cells adhering to a substrate. Our finding that this theory also applies to cells in suspension provides the foundation for a quantitative high-throughput measurement of cell mechanical properties with microfluidic devices.
authors.affiliation: Biophysics Group, Department of Physics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Janina R
authors.initials: JR
authors.lastname: Lange
authors.affiliation: Biophysics Group, Department of Physics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Steinwachs
authors.affiliation: Biophysics Group, Department of Physics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany; Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kolb
authors.affiliation: Biophysics Group, Department of Physics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Lena A
authors.initials: LA
authors.lastname: Lautscham
authors.affiliation: Max Planck Institute for the Science of Light, Erlangen, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Harder
authors.affiliation: Institute of Biological Chemistry, Biophysics and Bioengineering, Department of Physics, Heriot-Watt University, Edinburgh, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: Whyte
authors.affiliation: Biophysics Group, Department of Physics, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany. Electronic address: bfabry@biomed.uni-erlangen.de.
authors.forename: Ben
authors.initials: B
authors.lastname: Fabry
mesh_terms: D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D002468:Cell Physiological Phenomena / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D004867:Equipment Design; D005898:Glass / Q000737:chemistry; D006801:Humans; D056656:Lab-On-A-Chip Devices; D055595:Mechanical Phenomena; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D055616:Microtechnology / Q000295:instrumentation; D008962:Models, Theoretical; D011312:Pressure; D012212:Rheology