Computational model of polarized actin cables and cytokinetic actin ring formation in budding yeast

Tang, Haosu; Bidone, Tamara C.; Vavylonis, Dimitrios

doi:10.1002/cm.21258

Cited by 12 publications

(14 citation statements)

References 89 publications

(170 reference statements)

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“…Additionally, the need for torsional strain on the actin may affect the binding length scale and spacing between cross-linkers of the same type. It may be possible to incorporate these structural characteristics using other simulation frameworks (25,37,38).…”

Section: Discussionmentioning

confidence: 99%

Mechanical and kinetic factors drive sorting of F-actin cross-linkers on bundles

Freedman

Suarez

Winkelman

et al. 2019

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

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In cells, actin-binding proteins (ABPs) sort to different regions to establish F-actin networks with diverse functions, including filopodia used for cell migration and contractile rings required for cell division. Recent experimental work uncovered a competition-based mechanism that may facilitate spatial localization of ABPs: binding of a short cross-linker protein to 2 actin filaments promotes the binding of other short cross-linkers and inhibits the binding of longer cross-linkers (and vice versa). We hypothesize this sorting arises because F-actin is semiflexible and cannot bend over short distances. We develop a mathematical theory and lattice models encompassing the most important physical parameters for this process and use coarse-grained simulations with explicit cross-linkers to characterize and test our predictions. Our theory and data predict an explicit dependence of cross-linker separation on bundle polymerization rate. We perform experiments that confirm this dependence, but with an unexpected cross-over in dominance of one cross-linker at high growth rates to the other at slow growth rates, and we investigate the origin of this cross-over with further simulations. The nonequilibrium mechanism that we describe can allow cells to organize molecular material to drive biological processes, and our results can guide the choice and design of cross-linkers for engineered protein-based materials.

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Section: Discussionmentioning

confidence: 99%

Mechanical and kinetic factors drive sorting of F-actin cross-linkers on bundles

Freedman

Suarez

Winkelman

et al. 2019

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

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“…To generate a spatial pattern of inhibitors such as Rga4 and Rga6, which accumulate in "collar" or "corset" shapes around growing cell tips [36][37][38][39], we make the bold assumption that these inhibitors that we collectively call GAP II are also recruited to the plasma membrane through Cdc42-GTP (similar to GAP I ). We further assume that GAP II proteins that diffuse away from the cell tip convert to slowly-diffusing forms, possibly through binding to each other, thus accumulating away from the active region.…”

Section: Gap IImentioning

confidence: 99%

“…(iii) The two Cdc42 GEFs, Scd1 and Gef1, localize at cell tips, together with Cdc42-GTP [22,[30][31][32][33][34][35]. By contrast, three known Cdc42 GAPs establish an intriguing pattern, with Rga4 [36][37][38] and Rga6 [39] decorating primarily the cell sides while Rga3 accumulates primarily at the cell tips [40]. Fluorescence recovery after photobleaching (FRAP) studies indicate different dynamics of Rga6 at cell tips as compared to cell sides: the percent recovery at the cell sides is smaller than the tips over the same time period [39].…”

Section: Introductionmentioning

confidence: 99%

Fission Yeast Polarization: Modeling Cdc42 Oscillations, Symmetry Breaking, and Zones of Activation and Inhibition

Khalili

Lovelace

Rutkowski

et al. 2020

Cells

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Cells polarize for growth, motion, or mating through regulation of membrane-bound small GTPases between active GTP-bound and inactive GDP-bound forms. Activators (GEFs, GTP exchange factors) and inhibitors (GAPs, GTPase activating proteins) provide positive and negative feedbacks. We show that a reaction–diffusion model on a curved surface accounts for key features of polarization of model organism fission yeast. The model implements Cdc42 membrane diffusion using measured values for diffusion coefficients and dissociation rates and assumes a limiting GEF pool (proteins Gef1 and Scd1), as in prior models for budding yeast. The model includes two types of GAPs, one representing tip-localized GAPs, such as Rga3; and one representing side-localized GAPs, such as Rga4 and Rga6, that we assume switch between fast and slow diffusing states. After adjustment of unknown rate constants, the model reproduces active Cdc42 zones at cell tips and the pattern of GEF and GAP localization at cell tips and sides. The model reproduces observed tip-to-tip oscillations with periods of the order of several minutes, as well as asymmetric to symmetric oscillations transitions (corresponding to NETO “new end take off”), assuming the limiting GEF amount increases with cell size.

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“…In actin cables and the contractile ring, formin-nucleated actin filaments are crosslinked into long bundles with a length on the order of microns [ 3 – 5 ]. Computational models of these actin structures typically treat actin filaments as semi-flexible polymers that are connected by rigid segments [ 6 – 9 ]. In contrast, the organization of the actin network in actin patches formed during clathrin-mediated endocytosis is drastically different from that in actin cables or the contractile ring.…”

Section: Introductionmentioning

confidence: 99%

Structural organization and energy storage in crosslinked actin assemblies

Berro

2018

PLoS Comput Biol

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During clathrin-mediated endocytosis in yeast cells, short actin filaments (< 200nm) and crosslinking protein fimbrin assemble to drive the internalization of the plasma membrane. However, the organization of the actin meshwork during endocytosis remains largely unknown. In addition, only a small fraction of the force necessary to elongate and pinch off vesicles can be accounted for by actin polymerization alone. In this paper, we used mathematical modeling to study the self-organization of rigid actin filaments in the presence of elastic crosslinkers in conditions relevant to endocytosis. We found that actin filaments condense into either a disordered meshwork or an ordered bundle depending on filament length and the mechanical and kinetic properties of the crosslinkers. Our simulations also demonstrated that these nanometer-scale actin structures can store a large amount of elastic energy within the crosslinkers (up to 10kBT per crosslinker). This conversion of binding energy into elastic energy is the consequence of geometric constraints created by the helical pitch of the actin filaments, which results in frustrated configurations of crosslinkers attached to filaments. We propose that this stored elastic energy can be used at a later time in the endocytic process. As a proof of principle, we presented a simple mechanism for sustained torque production by ordered detachment of crosslinkers from a pair of parallel filaments.

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Computational model of polarized actin cables and cytokinetic actin ring formation in budding yeast

Cited by 12 publications

References 89 publications

Mechanical and kinetic factors drive sorting of F-actin cross-linkers on bundles

Mechanical and kinetic factors drive sorting of F-actin cross-linkers on bundles

Fission Yeast Polarization: Modeling Cdc42 Oscillations, Symmetry Breaking, and Zones of Activation and Inhibition

Structural organization and energy storage in crosslinked actin assemblies

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