Dynacortin contributes to cortical viscoelasticity and helps define the shape changes of cytokinesis

Girard, Kristine D.; Chaney, Charles A.; Delannoy, Michaël; Kuo, Scot C.; Robinson, Douglas N.

doi:10.1038/sj.emboj.7600167

Cited by 65 publications

(103 citation statements)

References 37 publications

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“…45 The knockdown efficiency of dynacortin by dyn-hp is >98%. 10 Consistent with previous results, myosin II null cells (deleted for the myosin II heavy chain (mhcA) gene, Fig. 4(f)) displayed a smaller slope (lower Young's modulus in Table I) compared to WT cells (Fig.…”

supporting

confidence: 79%

“…The former involves simplifying the cellular systems by the combination of genetic deletion or knockdown of nonessential genes and pharmacological inhibition of the function of certain proteins. 4,[10][11][12] The latter relies on the reconstitution of the actin cytoskeleton with purified or synthesized components in in vitro systems. [13][14][15][16][17][18][19][20][21] Previous measurements conducted with in vivo and in vitro systems suggest that the mechanical properties of the actin cortex depend on the force-dependent affinities of all of these proteins to F-actin as well as their concentrations.…”

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confidence: 99%

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Mimicking the mechanical properties of the cell cortex by the self-assembly of an actin cortex in vesicles

Luo

Srivastava

Ren

et al. 2014

Applied Physics Letters

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The composite of the actin cytoskeleton and plasma membrane plays important roles in many biological events. Here, we employed the emulsion method to synthesize artificial cells with biomimetic actin cortex in vesicles and characterized their mechanical properties. We demonstrated that the emulsion method provides the flexibility to adjust the lipid composition and protein concentrations in artificial cells to achieve the desired size distribution, internal microstructure, and mechanical properties. Moreover, comparison of the cortical elasticity measured for reconstituted artificial cells to that of real cells, including those manipulated using genetic depletion and pharmacological inhibition, strongly supports that actin cytoskeletal proteins are dominant over lipid molecules in cortical mechanics. Our study indicates that the assembly of biological systems in artificial cells with purified cellular components provides a powerful way to answer biological questions. The actin cortex is a thin sheet of actin meshwork formed by actin cytoskeletal proteins, including actin, actin crosslinkers (ACs), motor proteins, and other actin binding proteins (Fig. S1). [3][4][5] The plasma membrane is largely a lipid bilayer embedded with transmembrane proteins. The actin cortex and plasma membrane are connected by anchoring proteins. The composite of actin cytoskeleton and plasma membrane plays important roles in sensing mechanical stimuli and subsequently remodeling its own microstructure, which governs many essential cellular events such as migration and morphogenesis. [6][7][8][9] The cell shape changes in these events can be largely considered mechanical processes. Therefore, understanding the mechanical properties of the composite can provide deep insight into the nature of important biological phenomena.Currently, there are two complementary strategies for studying the mechanical properties of cells: the top-down and the bottom-up approaches. The former involves simplifying the cellular systems by the combination of genetic deletion or knockdown of nonessential genes and pharmacological inhibition of the function of certain proteins. 4,[10][11][12] The latter relies on the reconstitution of the actin cytoskeleton with purified or synthesized components in in vitro systems. [13][14][15][16][17][18][19][20][21] Previous measurements conducted with in vivo and in vitro systems suggest that the mechanical properties of the actin cortex depend on the force-dependent affinities of all of these proteins to F-actin as well as their concentrations. Despite the numerous experiments conducted in live cells, only a limited number of genes and proteins can be deleted or inhibited simultaneously, and when expressing genes of interest in cells, it can be difficult to control expression precisely. On the other hand, numerous proteins can be added in precisely controlled concentrations to in vitro reconstitution systems, though this can be labor intensive. One type of in vitro assay is to assemble the actin meshwork into a 2D flat she...

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confidence: 79%

mentioning

confidence: 99%

Mimicking the mechanical properties of the cell cortex by the self-assembly of an actin cortex in vesicles

Luo

Srivastava

Ren

et al. 2014

Applied Physics Letters

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“…Control strains carried the parental plasmid, pLD1A15SN, which allowed all cells to be grown under identical media conditions (19). To generate the RacE͞dynacortin and myosin II͞dynacortin double-mutant combinations, RacE and myosin II mutant strains were transformed with a dynacortin hairpin (dynhp) construct (15). No dynacortin protein was detectable in dynhp cells by Western immunodetection by using antidynacortin antibodies as described and quantified in ref.…”

Section: Methodsmentioning

confidence: 99%

“…1A). Each protein plays an important role in cytokinesis and cortical mechanics (7,(13)(14)(15)(16)(17)(18). Each mutant strain follows a unique time-dependent trajectory of furrow ingression.…”

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confidence: 99%

Balance of actively generated contractile and resistive forces controls cytokinesis dynamics

Zhang

Robinson

2005

Proc. Natl. Acad. Sci. U.S.A.

112

182

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Cytokinesis, the fission of a mother cell into two daughter cells, is a simple and dramatic cell shape change. Here, we examine the dynamics of cytokinesis by using a combination of microscopy, dynamic measurements, and genetic analysis. We find that cytokinesis proceeds through a single sequence of shape changes, but the kinetics of the transformation from one shape to another differs dramatically between strains. We interpret the measurements in a simple and quantitative manner by using a previously uncharacterized analytic model. From the analysis, wild-type cytokinesis appears to proceed through an active, extremely regulated process in which globally distributed proteins generate resistive forces that slow the rate of furrow ingression. Finally, we propose that, in addition to myosin II, a Laplace pressure, resulting from material properties and the geometry of the dividing cell, generates force to help drive furrow ingression late in cytokinesis.cell dynamics ͉ myosin II ͉ dynacortin ͉ RacE ͉ cell mechanics

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“…Furthermore, in cells, active processes that require ATP hydrolysis can also stir these elements, promoting the emergence of a viscous-like character (11,12). Cell-cortex mechanics at these scales have been analyzed in Dictyostelium (4,13,14) and in multiple mammalian cell types (15,16). In these low-force regimes, cells are predominantly elastic with a mechanical phase angle of~10-15 .…”

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confidence: 99%

Mechanochemical Signaling Directs Cell-Shape Change

Schiffhauer

Robinson

2017

Biophysical Journal

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For specialized cell function, as well as active cell behaviors such as division, migration, and tissue development, cells must undergo dynamic changes in shape. To complete these processes, cells integrate chemical and mechanical signals to direct force production. This mechanochemical integration allows for the rapid production and adaptation of leading-edge machinery in migrating cells, the invasion of one cell into another during cell-cell fusion, and the force-feedback loops that ensure robust cytokinesis. A quantitative understanding of cell mechanics coupled with protein dynamics has allowed us to account for furrow ingression during cytokinesis, a model cell-shape-change process. At the core of cell-shape changes is the ability of the cell's machinery to sense mechanical forces and tune the force-generating machinery as needed. Force-sensitive cytoskeletal proteins, including myosin II motors and actin cross-linkers such as a-actinin and filamin, accumulate in response to internally generated and externally imposed mechanical stresses, endowing the cell with the ability to discern and respond to mechanical cues. The physical theory behind how these proteins display mechanosensitive accumulation has allowed us to predict paralogspecific behaviors of different cross-linking proteins and identify a zone of optimal actin-binding affinity that allows for mechanical stress-induced protein accumulation. These molecular mechanisms coupled with the mechanical feedback systems ensure robust shape changes, but if they go awry, they are poised to promote disease states such as cancer cell metastasis and loss of tissue integrity.The concept ''form begets function begets form'' provides an excellent foundation for understanding the behavior of biological systems. Even specialized cells, the smallest unit of complex living systems, perform all of the necessary functions of an organism by assuming distinct shapes, mechanical properties, and physical behaviors. Different cell types use a common set of cytoskeletal elements to provide precise physical support for their distinct functions. For example, red blood cells and neurons have very different shapes that allow them to perform their specific roles. However, they both utilize alternating patterns of actin and spectrin to form cortices with appropriate viscous and elastic properties, albeit in different structural arrangements. Perturbations to this structural network cause a breakdown in the mechanical properties, or the form, of these cells, which inhibits cell function (1,2).Fascinatingly, the physical properties of cells are both determined and acted upon by the cytoskeletal apparatus. Cells are capable of modifying their own physical properties and driving changes in cell shape in response to internal and external chemical and mechanical stimuli. These modifications occur through the remodeling of the cell cortex, the network of cytoskeletal proteins directly under the plasma membrane. Much progress has been made recently in deciphering how chemical signa...

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Dynacortin contributes to cortical viscoelasticity and helps define the shape changes of cytokinesis

Cited by 65 publications

References 37 publications

Mimicking the mechanical properties of the cell cortex by the self-assembly of an actin cortex in vesicles

Mimicking the mechanical properties of the cell cortex by the self-assembly of an actin cortex in vesicles

Balance of actively generated contractile and resistive forces controls cytokinesis dynamics

Mechanochemical Signaling Directs Cell-Shape Change

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