  The nucleus of the eukaryotic cell functions amidst active cytoskeletal
filaments, but its response to the stresses carried by these filaments is
largely unexplored. We report here the results of studies of the translational
and rotational dynamics of the nuclei of single fibroblast cells, with the
effects of cell migration suppressed by plating onto fibronectin-coated
micro-fabricated patterns. Patterns of the same area but different shapes
and/or aspect ratio were used to study the effect of cell geometry on the
dynamics. On circles, squares and equilateral triangles, the nucleus undergoes
persistent rotational motion, while on high-aspect-ratio rectangles of the same
area it moves only back and forth. The circle and the triangle showed
respectively the largest and the smallest angular speed. We show that our
observations can be understood through a hydrodynamic approach in which the
nucleus is treated 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 persistence time 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 a generic property that cells must balance by
specific mechanisms in order to maintain nuclear homeostasis.
