The microstructure of the nucleus, one of the most studied but least understood cellular organelles, is the subject of much debate. Through the use of particle nanotracking, we detect and quantify the micro-organization as well as the viscoelastic properties of the intranuclear region in single, live, interphase somatic cells. We find that the intranuclear region is much stiffer than the cytoplasm; it is also more elastic than viscous, which reveals that the intranuclear region displays an unexpectedly strong solid-like behavior. The mean shear viscosity and elasticity of the intranuclear region of Swiss 3T3 fibroblasts are 520 Poise (P) and 180 dyn/cm2, respectively. These measurements determine a lower bound of the propulsive forces (3-15 picoNewton) required for nuclear organelles such as promyelocytic-leukemia bodies to undergo processive transport within the nucleus by overcoming friction forces set by the intranuclear viscosity. Dynamic analysis of the spontaneous movements of nanospheres embedded in the nucleus reveals the presence of putative transient nuclear microdomains of mean size 290±50 nm, which are mostly absent in the cytoplasm. The strong elastic character and micro-organization of the intranuclear region revealed by particle nanotracking analysis may help the nucleus to preserve its structural coherence. These studies also highlight the difference between the low interstitial nucleoplasmic viscosity, which controls the transport of nuclear proteins and molecules, and the much higher mesoscale viscosity, which affects the diffusion and directed transport of nuclear organelles and re-organization of interphase chromosomes.

Cell migration is a highly coordinated process that occurs through the translation of biochemical signals into specific biomechanical events. The biochemical and structural properties of the proteins involved in cell motility, as well as their subcellular localization, have been studied extensively. However, how these proteins work in concert to generate the mechanical properties required to produce global motility is not well understood. Using intracellular microrheology and a fibroblast scratch-wound assay, we show that cytoskeleton reorganization produced by motility results in mechanical stiffening of both the leading lamella and the perinuclear region of motile cells. This effect is significantly more pronounced in the leading edge, suggesting that the mechanical properties of migrating fibroblasts are spatially coordinated. Disruption of the microtubule network by nocodazole treatment results in the arrest of cell migration and a loss of subcellular mechanical polarization; however, the overall mechanical properties of the cell remain mostly unchanged. Furthermore, we find that activation of Rac and Cdc42 in quiescent fibroblasts elicits mechanical behavior similar to that of migrating cells. We conclude that a polarized mechanics of the cytoskelton is essential for directed cell migration and is coordinated through microtubules. INTRODUCTIONCell migration is a cellular process that plays a critical role in health and disease, including embryogenesis, wound healing, immune response, and tissue development (Lauffenburger and Horwitz, 1996;Mitchison and Cramer, 1996;Pollard and Borisy, 2003). It is a highly regulated and coordinated process, which occurs through a myriad of signaling and structural proteins that orchestrate spatiotemporal reorganization of the actin cytoskeleton. Abnormal and/or unregulated cell motile behavior is known to contribute to several potentially fatal illnesses, including vascular disease and cancer (Ridley et al., 2003).Cell migration can be modeled as a repetitive, multistep process that begins with the establishment of spatial polarity and extension of membrane protrusions in the direction of movement. Newly formed protrusions are subsequently stabilized through firm adhesions to the underlying substrate and initiate contractile mechanisms that generate net forward motion and retraction of the trailing edge (Lauffenburger and Horwitz, 1996;Mitchison and Cramer, 1996;Pollard and Borisy, 2003). Every step of this cycle critically depends on the timely assembly, disassembly, and reorganization of actin filament structures that are mediated by members of the Rho family of small GTPases (Nobes and Hall, 1999). Overexpression of dominant negative variants of Rac and Cdc42 in fibroblasts reveals that Rac is necessary for membrane protrusion and the formation of wide lamella, whereas Cdc42 is required for the maintenance of cell polarity (Nobes and Hall, 1999).Research over the past three decades has identified a myriad of structural and signaling proteins that regulate cell motility. ...

A B S T R A C TN-body simulations show that when infall reorientates the outer parts of a galactic halo by several degrees per Gyr, a self-gravitating disc that is embedded in the halo develops an integral-sign warp that is comparable in amplitude to observed warps. Studies of angularmomentum acquisition suggest that the required rate of halo reorientation is realistic for galaxies like the Milky Way.

Possible orbital histories of the Sgr dwarf galaxy are explored. A special‐purpose N‐body code is used to construct the first models of the Milky Way–Sgr dwarf system in which both the Milky Way and the Sgr dwarf are represented by full N‐body systems and followed for a Hubble time. These models are used to calibrate a semi‐analytic model of the Sgr dwarf's orbit that enables us to explore a wider parameter space than is accessible to the N‐body models. We conclude that the extant data on the Sgr dwarf are compatible with a wide range of orbital histories. At one extreme the Sgr dwarf initially possesses ∼1011 M⊙ and starts from a Galactocentric distance RD(0)≳200 kpc. At the other extreme the Sgr dwarf starts with ∼109 M⊙ and RD(0)∼60 kpc, similar to its present apocentric distance. In all cases the Sgr dwarf is initially dark matter dominated and the current velocity dispersion of the Sgr dwarf's dark matter is tightly constrained to be 21±2 km s−1. This number is probably compatible with the smaller measured dispersion of the Sgr dwarf's stars because of (i) the dynamical difference between dark and luminous matter, and (ii) velocity anisotropy.

A B S T R A C TWe study the persistence of warps in galactic discs in the presence of massive haloes. A disc is approximated by a set of massive rings, while a halo is represented by a conventional n-body simulation. We confirm the conclusion of Nelson & Tremaine that a halo responds strongly to an embedded precessing disc. This response invalidates the approximations made in the derivation of classical 'modified tilt' modes. We show that the response of the halo causes the line of nodes of a disc that starts from a modified tilt mode to wind up within a few dynamical times. We explain this finding in terms of the probable spectrum of true normal modes of a combined disc-halo system. The key physical point is that in each radial range the halo rapidly aligns with the disc, so calculations based on the assumption that, in the presence of a warped disc, the halo retains a regular spheroidal structure are based on a fatally flawed assumption.