title: Power-law rheology of isolated nuclei with deformation mapping of nuclear substructures.
abstract: Force-induced changes in genome expression as well as remodeling of nuclear architecture in development and disease motivate a deeper understanding of nuclear mechanics. Chromatin and green fluorescent protein-lamin B dynamics were visualized in a micropipette aspiration of isolated nuclei, and both were shown to contribute to viscoelastic properties of the somatic cell nucleus. Reversible swelling by almost 200% in volume, with changes in salt, demonstrates the resilience and large dilational capacity of the nuclear envelope, nucleoli, and chromatin. Swelling also proves an effective way to separate the mechanical contributions of nuclear elements. In unswollen nuclei, chromatin is a primary force-bearing element, whereas swollen nuclei are an order of magnitude softer, with the lamina sustaining much of the load. In both cases, nuclear deformability increases with time, scaling as a power law-thus lacking any characteristic timescale-when nuclei are either aspirated or indented by atomic force microscopy. The nucleus is stiff and resists distortion at short times, but it softens and deforms more readily at longer times. Such results indicate an essentially infinite spectrum of timescales for structural reorganization, with implications for regulating genome expression kinetics.
authors.affiliation: Johns Hopkins University, Baltimore, MD 21202, USA.
authors.forename: Kris Noel
authors.initials: KN
authors.lastname: Dahl
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Engler
authors.forename: J David
authors.initials: JD
authors.lastname: Pajerowski
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Discher
mesh_terms: D000818:Animals; D002460:Cell Line; D022003:Cell Nucleus Structures / Q000502:physiology* / Q000648:ultrastructure; D048429:Cell Size; D002522:Chlorocebus aethiops; D003198:Computer Simulation; D004548:Elasticity; D004847:Epithelial Cells / Q000502:physiology*; D044085:Microfluidics / Q000379:methods*; D018625:Microscopy, Atomic Force / Q000379:methods*; D008954:Models, Biological; D011312:Pressure; D013314:Stress, Mechanical; D014783:Viscosity