The Reorientation of Cell Nucleus Promotes the Establishment of Front–Rear Polarity in Migrating Fibroblasts

Maninová, Miloslava; Klímová, Zuzana; Parsons, J. Thomas; Weber, Michael J.; Iwanicki, Marcin P.; Vomastek, Tomáš

doi:10.1016/j.jmb.2013.02.034

Cited by 35 publications

(63 citation statements)

References 74 publications

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“…Both translational and rotational movement of the nucleus during cell migration has been reported in the literature101115161718 for many cell types including NIH3T3 which was used in all our experiments. For completeness, we document nuclear dynamics during migration here as well.…”

Section: Resultsmentioning

confidence: 99%

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Actomyosin contractility rotates the cell nucleus

Kumar¹,

Maitra

Sumit³

et al. 2014

Sci Rep

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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.

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Section: Resultsmentioning

confidence: 99%

“…It has long been known that the nucleus both translates and rotates in the cytoplasm in a variety of experimental situations10111213141516171819. While a number of molecular players including actin have been implicated in this context12349121520, we offer here a generic hydrodynamic understanding based on actomyosin contractility.…”

mentioning

confidence: 99%

Actomyosin contractility rotates the cell nucleus

Kumar¹,

Maitra

Sumit³

et al. 2014

Sci Rep

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“…A body of research has shown that stress fibres couple nuclear shape to cell shape 13, 14 and are involved in modulating nuclear morphology of differentiating cells 15 as well as the organisation of laminA/C 16 . On the other hand, the microtubule network has been shown to support nuclear rotation and repositioning, highlighting its mechanical link with the nucleus via microtubule-associated motor proteins and members of the nesprin family 17, 18 . Finally, the intermediate filament network has been recently proposed as an additional player in the mechanical regulation of nuclear shape in keratin-rich cells 19 .…”

Section: Introductionmentioning

confidence: 99%

Actomyosin and vimentin cytoskeletal networks regulate nuclear shape, mechanics and chromatin organization

Keeling

Flores

Dodhy

et al. 2017

Sci Rep

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The regulation of nuclear state by the cytoskeleton is an important part of cellular function. Actomyosin stress fibres, microtubules and intermediate filaments have distinct and complementary roles in integrating the nucleus into its environment and influencing its mechanical state. However, the interconnectedness of cytoskeletal networks makes it difficult to dissect their individual effects on the nucleus. We use simple image analysis approaches to characterize nuclear state, estimating nuclear volume, Poisson’s ratio, apparent elastic modulus and chromatin condensation. By combining them with cytoskeletal quantification, we assess how cytoskeletal organization regulates nuclear state. We report for a number of cell types that nuclei display auxetic properties. Furthermore, stress fibres and intermediate filaments modulate the mechanical properties of the nucleus and also chromatin condensation. Conversely, nuclear volume and its gross morphology are regulated by intracellular outward pulling forces exerted by myosin. The modulation exerted by the cytoskeleton onto the nucleus results in changes that are of similar magnitude to those observed when the nucleus is altered intrinsically, inducing chromatin decondensation or cell differentiation. Our approach allows pinpointing the contribution of distinct cytoskeletal proteins to nuclear mechanical state in physio- and pathological conditions, furthering our understanding of a key aspect of cellular behaviour.

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“…Previously, we have shown that during the polarization of RAT2 fibroblasts, the nucleus undergoes temporal rotational movement which aligns the nuclear axis with the axis of migration. Nuclear reorientation requires both integrin attachment to extracellular matrix and LINC complex suggesting that adhesions‐associated cytoskeleton and LINC complex transmit force from substratum to the nucleus . We have hypothesized that contractile actin fibers linking the nucleus with adhesions at the leading edge could drive the nuclear reorientation .…”

Section: Introductionmentioning

confidence: 99%

Dorsal stress fibers, transverse actin arcs, and perinuclear actin fibers form an interconnected network that induces nuclear movement in polarizing fibroblasts

Maninová

Vomastek

2016

The FEBS Journal

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In polarized motile cells, stress fibers display specific three-dimensional organization. Ventral stress fibers, attached to focal adhesions at both ends, are restricted to the basal side of the cell and nonprotruding cell sides. Dorsal fibers, transverse actin arcs, and perinuclear actin fibers emanate from protruding cell front toward the nucleus and toward apical side of the cell. Perinuclear cap fibers further extend above the nucleus, associate with nuclear envelope through LINC (linker of nucleoskeleton and cytoskeleton) complex and terminate in focal adhesions at cell rear. How are perinuclear actin fibers formed is poorly understood. We show that the formation of perinuclear actin fibers requires dorsal stress fibers that polymerize from focal adhesions at leading edge, and transverse actin arcs that are interconnected with dorsal fibers in spots rich in a-actinin-1. During cell polarization, the interconnected dorsal fibers and transverse arcs move from leading edge toward dorsal side of the cell. As they move, transverse arcs associate with one end of stress fibers present at nonprotruding cell sides, move them above the nucleus thus forming perinuclear actin fibers. Furthermore, the formation of perinuclear actin fibers induces temporal rotational movement of the nucleus resulting in nuclear reorientation to the direction of migration. These results suggest that the network of dorsal fibers, transverse arcs, and perinuclear fibers transfers mechanical signal between the focal adhesions and nuclear envelope that regulates the nuclear reorientation in polarizing cells. IntroductionIn migrating cells, actin forms diverse types of stress fibers that differ in morphological, structural, and contractile characteristics [1][2][3][4]. Contractile ventral or basal stress fibers lie along the base of the cell usually parallel to the direction of migration and they are attached to the focal adhesions at both ends. Ventral stress fibers are rich in a-actinin and myosin that crosslink the actin fibers and mediate their contractility. Ventral stress fibers are involved in diverse cellular functions such as maturation of adhesions, formation of nonprotrusive cell rear during cell spreading [5], establishment of front-rear polarity [6][7][8], generation of traction forces, retraction of the trailing edge [9,10], and regulation of cell shape on compliant substrates [11]. Contractile stress fibers also participate in remodeling of extracellular matrix [12].In contrast to ventral stress fibers that are confined to the basal side of the cell, an array of dorsal fibers, Abbreviations ECM, extracellular matrix; KASH, Klarsicht/ANC-1/Syne-1 homology; LINC, linker of nucleoskeleton and cytoskeleton; SIM, structured illumination microscopy. 3676

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The Reorientation of Cell Nucleus Promotes the Establishment of Front–Rear Polarity in Migrating Fibroblasts

Cited by 35 publications

References 74 publications

Actomyosin contractility rotates the cell nucleus

Actomyosin contractility rotates the cell nucleus

Actomyosin and vimentin cytoskeletal networks regulate nuclear shape, mechanics and chromatin organization

Dorsal stress fibers, transverse actin arcs, and perinuclear actin fibers form an interconnected network that induces nuclear movement in polarizing fibroblasts

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