title: Imaging viscoelastic properties of live cells by AFM: power-law rheology on the nanoscale.
abstract: We developed force clamp force mapping (FCFM), an atomic force microscopy (AFM) technique for measuring the viscoelastic creep behavior of live cells with sub-micrometer spatial resolution. FCFM combines force-distance curves with an added force clamp phase during tip-sample contact. From the creep behavior measured during the force clamp phase, quantitative viscoelastic sample properties are extracted. We validate FCFM on soft polyacrylamide gels. We find that the creep behavior of living cells conforms to a power-law material model. By recording short (50-60 ms) force clamp measurements in rapid succession, we generate, for the first time, two-dimensional maps of power-law exponent and modulus scaling parameter. Although these maps reveal large spatial variations of both parameters across the cell surface, we obtain robust mean values from the several hundreds of measurements performed on each cell. Measurements on mouse embryonic fibroblasts show that the mean power-law exponents and the mean modulus scaling parameters differ greatly among individual cells, but both parameters are highly correlated: stiffer cells consistently show a smaller power-law exponent. This correlation allows us to distinguish between wild-type cells and cells that lack vinculin, a dominant protein of the focal adhesion complex, even though the mean values of viscoelastic properties between wildtype and knockout cells did not differ significantly. Therefore, FCFM spatially resolves viscoelastic sample properties and can uncover subtle mechanical signatures of proteins in living cells.
authors.affiliation: Institute of Applied Physics, University of Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany. tilman.schaeffer@uni-tuebingen.de.
authors.forename: Fabian M
authors.initials: FM
authors.lastname: Hecht
authors.affiliation: Institute of Applied Physics, University of Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany. tilman.schaeffer@uni-tuebingen.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Rheinlaender
authors.affiliation: Institute of Applied Physics, University of Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany. tilman.schaeffer@uni-tuebingen.de.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schierbaum
authors.affiliation: Department of Physics, University of Erlangen-Nuremberg, Henkestraße 91, 91052 Erlangen, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Goldmann
authors.affiliation: Department of Physics, University of Erlangen-Nuremberg, Henkestraße 91, 91052 Erlangen, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Fabry
authors.affiliation: Institute of Applied Physics, University of Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany. tilman.schaeffer@uni-tuebingen.de.
authors.forename: Tilman E
authors.initials: TE
authors.lastname: Schäffer
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D004548:Elasticity; D004622:Embryo, Mammalian / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D018625:Microscopy, Atomic Force; D012212:Rheology; D016596:Vinculin / Q000235:genetics / Q000378:metabolism; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D016596:Vinculin; D000099166:Polyacrylamides