title: A microfluidic device for characterizing nuclear deformations.
abstract: Cell nuclei experience and respond to a wide range of forces, both in vivo and in vitro. In order to characterize the nuclear response to physical stress, we developed a microfluidic chip and used it to apply mechanical stress to live cells and measure their nuclear deformability. The device design is optimized for the detection of both nucleus and cytoplasm, which can then be conveniently quantified using a custom-written Matlab program. We measured nuclear sizes and strains of embryonic stem cells, for which we observed negative Poisson ratios in the nuclei. In addition, we were able to detect changes in the nuclear response after treatment with actin depolymerizing and chromatin decondensing agents. Finally, we showed that the device can be used for biologically relevant high-resolution confocal imaging of cells under compression. Thus, the device presented here allows for accurate physical phenotyping at high throughput and has the potential to be applied to a range of cell types.
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK. kc370@cam.ac.uk.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Hodgson
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK. kc370@cam.ac.uk and Wellcome Trust/Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge CB3 0ES, UK.
authors.forename: Christophe M
authors.identifier: 0000-0001-9038-1094
authors.initials: CM
authors.lastname: Verstreken
authors.affiliation: Wellcome Trust/Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge CB3 0ES, UK.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Fisher
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK. kc370@cam.ac.uk.
authors.forename: Ulrich F
authors.identifier: 0000-0003-3188-5414
authors.initials: UF
authors.lastname: Keyser
authors.affiliation: Department of Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, Devon EX4, UK. s.pagliara@exeter.ac.uk.
authors.forename: Stefano
authors.initials: S
authors.lastname: Pagliara
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, Cambridge CB3 0HE, UK. kc370@cam.ac.uk and Wellcome Trust/Medical Research Council Cambridge Stem Cell Institute and Department of Clinical Neurosciences, University of Cambridge, Cambridge CB3 0ES, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Chalut
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000502:physiology*; D053144:Cell Nucleus Shape / Q000502:physiology*; D002478:Cells, Cultured; D056656:Lab-On-A-Chip Devices; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D013234:Stem Cells