Actomyosin contractility rotates the cell nucleus

Abstract

The cell nucleus functions amidst active cytoskeletal filaments, but its response to their contractile stresses is largely unexplored. We study the dynamics of the nuclei of single fibroblasts, with cell migration suppressed by plating onto micro-fabricated patterns. We find the nucleus undergoes noisy but coherent rotational motion. We account for this observation through a hydrodynamic approach, treating the nucleus as a highly viscous inclusion residing in a less viscous fluid of orientable filaments endowed with active stresses. Lowering actin contractility selectively by introducing blebbistatin at low concentrations drastically reduced the speed and coherence of the angular motion of the nucleus. Time-lapse imaging of actin revealed a correlated hydrodynamic flow around the nucleus, with profile and magnitude consistent with the results of our theoretical approach. Coherent intracellular flows and consequent nuclear rotation thus appear to be an intrinsic property of cells.

Generation of stationary and moving vortices in active polar fluids in the planar Taylor-Couette geometry

“…In vitro, cytoskeletal filaments and molecular motors can self-organize into vortices [3,7,8] as well as asters [3,9], where all filaments originate from a common center and point radially outwards. In vivo, immobilized fibroblasts have been observed to generate rotational flows that set the cell nucleus into rotation [10]. The interaction of many point defects, their generation and annihilation can lead to apparent spatio-temporal chaos (or active turbulence) even at low Reynolds numbers as has been reported for bacterial suspensions [11] and in vitro assays of cytoskeletal filaments and molecular motors [12].…”

“…To this end we consider an active polar fluid in the Taylor-Couette geometry, that is, in the interstitial space between two coaxial cylinders, which we take to be immobile. The geometry is motivated on one hand by experimental works that analyzed spontaneous flows in annular [3] or circular dishes [5,6] or in the space between the nucleus and the plasma membrane of fibroblasts [10]. On the other hand this geometry naturally leads to a spontaneous shear flow of active fluids, which can be conveniently analysed for instabilities.…”

Nuclear Positioning and Its Translational Dynamics Are Regulated by Cell Geometry

“…Numerous diseases resulting from genetic alterations in the proteins involved in nuclear movement confirm the significance of proper nuclear positioning (12,13). Cellular geometry has been shown to impinge on gene expression and nuclear morphology, orientation, rotational dynamics, and deformability (14)(15)(16)(17) in studies utilizing micropatterned cells of defined shapes and spread area. However, in well-defined boundary conditions that mimic tissue environments, nuclear positioning and its translational dynamics in single cells has not been studied.…”

Nanoscale histone localization in live cells reveals reduced chromatin mobility in response to DNA damage

“…With single-particle tracking (SPT) approaches, time-lapse images are registered to compensate for cellular movements, often using the center of the nucleus, the nuclear envelope or nuclear bodies as offsets. Registration, however, adds uncertainties to the measurements, because cell nuclei rotate and distort (Kumar et al, 2014). Alternatively, it is possible using paired-particle tracking (PPT) to convert molecular dynamics from two-dimensional (2D) imaging planes into 1D motions that do not depend on cell movements (Heun et al, 2001;Vazquez et al, 2001).…”