Extensile motor activity drives coherent motions in a model of interphase chromatin

Abstract

The 3D spatiotemporal organization of the human genome inside the cell nucleus remains a major open question in cellular biology. In the time between two cell divisions, chromatin—the functional form of DNA in cells—fills the nucleus in its uncondensed polymeric form. Recent in vivo imaging experiments reveal that the chromatin moves coherently, having displacements with long-ranged correlations on the scale of micrometers and lasting for seconds. To elucidate the mechanism(s) behind these motions, we develop a coarse-grained active polymer model where chromatin is represented as a confined flexible chain acted upon by molecular motors that drive fluid flows by exerting dipolar forces on the system. Numerical simulations of this model account for steric and hydrodynamic interactions as well as internal chain mechanics. These demonstrate that coherent motions emerge in systems involving extensile dipoles and are accompanied by large-scale chain reconfigurations and nematic ordering. Comparisons with experiments show good qualitative agreement and support the hypothesis that self-organizing long-ranged hydrodynamic couplings between chromatin-associated active motor proteins are responsible for the observed coherent dynamics.

Non-equilibrium effects of molecular motors on polymers

“…10 While molecular motors can now be readily investigated using single-molecule techniques, [11][12][13] the emergent properties of systems where a collection of motors interact on, and through, their target polymer substrate remain poorly studied. 14,15 Here we propose a coarse-grained computational model to describe the action of generic molecular motors on polymers with the aim of improving our understanding of the effects of ATP-consuming translocating machineries on the conformational and dynamic properties of their target substrates. Within our model, motors undergo free diffusion in 3-D until they encounter the polymer, at which point they become ''bound'' to it via an attractive interaction.…”

“…To our knowledge our work is the first to explicitly treat discrete motors that track along a polymer in a fully 3-D system. A number of recent studies [14][15][16][17][18][19][20] have considered a chain of beads, where each bead experiences an active force, either directed along the chain bonds 17,18,20 or in a direction independent of the chain. 14,19 These works have mainly focused on regimes of different behaviour at different levels of activity (e.g., transitions from active translation to rotational motion 17 or to spiral configurations 18 have been observed -for a review see ref.…”

Swirling Instability of the Microtubule Cytoskeleton

“…As with any such spontaneous breaking of symmetry, both left-and righthand configurations are possible; the choice between the two is dictated by initial conditions. This transition is reminiscent of the self-organized rotation of cytoplasmic droplets extracted from plants [39] and the spiral vortex state of confined bacterial suspensions [40], both modeled as suspensions of stresslets [41][42][43].…”

Dynamics as a cause for the nanoscale organization of the genome

“…Our results suggest that closed chromatin is in fact a very active environment as further supported by the fact that a number of Active Effectors are known to be key determinants of closed chromatin assembly and function 10,51 . In addition, active processes have been shown experimentally 52,53 to drive coherent motion of chromatin 15,16 .…”