Morphological Transformation and Force Generation of Active Cytoskeletal Networks

Bidone, Tamara C.; Jung, Wonyeong; Maruri, Daniel P.; Borau, Carlos; Kamm, Roger D.; Kim, Taeyoon

doi:10.1371/journal.pcbi.1005277

Cited by 52 publications

(51 citation statements)

References 38 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of similar importance is the question of how myosin motors drive constriction. Recent work has demonstrated that dynamic end-tracking crosslinking can drive constriction (Mendes Pinto et al, 2012;Oelz et al, 2015), but a role for motoring activity has not been fully discounted (Zumdieck et al, 2007;Oelz et al, 2015;Bidone et al, 2017). Our in silico findings that motordead myosin-like ensembles can drive ring closure as long as they can track depolymerizing actin fiber ends ( Figure 3B) support the idea that dynamic crosslinking of treadmilling actin drives contraction.…”

Section: Discussionsupporting

confidence: 77%

Crosslinkers both drive and brake cytoskeletal remodeling and furrowing in cytokinesis

Descovich

Cortes

Ryan

et al. 2017

Preprint

View full text Add to dashboard Cite

Cytokinesis and other cell shape changes are driven by the actomyosin contractile cytoskeleton.The molecular rearrangements that bring about contractility in non-muscle cells are currently debated. Specifically, both filament sliding by myosin motors, as well as cytoskeletal crosslinking by myosins and non-motor crosslinkers, are thought to promote contractility. Here, we examined how the abundance of motor and non-motor crosslinkers controls the speed of cytokinetic furrowing. We built a minimal model to simulate the contractile dynamics of the C. elegans zygote cytokinetic ring. This model predicted that intermediate levels of non-motor crosslinkers would allow maximal contraction speed, which we found to be the case for the scaffold protein anillin, in vivo. Our model also demonstrated a non-linear relationship between the abundance of motor ensembles and contraction speed. In vivo, thorough depletion of non-muscle myosin II delayed furrow initiation, slowed F-actin alignment, and reduced maximum contraction speed, but partial depletion allowed faster-than-expected kinetics. Thus, both motor and non-motor crosslinkers promote cytokinetic ring closure when present at low levels, but act as a brake when present at higher levels. Together, our findings extend the growing appreciation for the roles of crosslinkers, but reveal that they not only drive but also brake cytoskeletal remodeling.

show abstract

Section: Discussionsupporting

confidence: 77%

Crosslinkers both drive and brake cytoskeletal remodeling and furrowing in cytokinesis

Descovich

Cortes

Ryan

et al. 2017

Preprint

View full text Add to dashboard Cite

show abstract

“…At the same time, filament turnover provides an effective way to dissipate local resistance to the rapid remodeling of actin networks that underlies flow and filament realignment (McFadden et al, 2017). Indeed, in a network of cross-linked filaments undergoing axial compression, filaments cannot realign without some degree of local filament buckling or inter-filament sliding (Bidone et al, 2017;Murrell et al, 2015). Thus, FGFA provides a way to maintain a selective memory of network deformation, while maintaining filament homeostasis and allowing rapid dissipation of local resistance to network deformation.…”

Section: Discussionmentioning

confidence: 99%

Existing actin filaments orient new filament growth to provide structural memory of filament alignment during cytokinesis

Munro

2020

Preprint

View full text Add to dashboard Cite

During cytokinesis, animal cells rapidly remodel the equatorial cortex to build an aligned array of actin filaments called the contractile ring. Local reorientation of filaments by equatorial contraction is thought to underlie the emergence of filament alignment during ring assembly.Here, combining single molecule analysis and modeling in one-cell C. elegans embryos, we show that filaments turnover is far too fast for reorientation of single filaments by equatorial contraction/cortex compression to explain the observed alignment, even if favorably oriented filaments are selectively stabilized. Instead, by tracking single Formin/CYK-1::GFP speckles to monitor local filament assembly, we identify a mechanism that we call filament-guided filament assembly (FGFA), in which existing filaments serve as templates to guide/orient the growth of new filaments. We show that FGFA sharply increases the effective lifetime of filament orientation, providing structural memory that allows slow equatorial contraction to build and maintain highly aligned filament arrays, despite rapid turnover of individual filaments.

show abstract

“…Observation of actin filament microstructure changes under these two mechanisms requires super-resolution and ultra-fast imaging, which is not achievable using our present experimental methods. Prior computational models have investigated actin bundles generation and remodeling due to slower biochemical reactions (32)(33)(34)(35)(36), but how external stimuli induce the active formation of actin bundles is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Tensile Force Induced Cytoskeletal Reorganization: Mechanics Before Chemistry

et al. 2020

Preprint

View full text Add to dashboard Cite

Understanding cellular remodeling in response to mechanical stimuli is a critical step in elucidating mechano-activation of biochemical signaling pathways. Experimental evidence indicates that external stress-induced subcellular adaptation is accomplished through dynamic cytoskeletal reorganization. To study the interactions between subcellular structures involved in transducing mechanical signals, we combined experimental and computational simulations to evaluate real-time mechanical adaptation of the actin cytoskeletal network. Actin cytoskeleton was imaged at the same time as an external tensile force was applied to live vascular smooth muscle cells using a fibronectin-functionalized atomic force microscope probe. In addition, we performed computational simulations of active cytoskeletal networks under a tensile external force. The experimental data and simulation results suggest that mechanical structural adaptation occurs before chemical adaptation during filament bundle formation: actin filaments first align in the direction of the external force, initializing anisotropic filament orientations, then the chemical evolution of the network follows the anisotropic structures to further develop the bundle-like geometry. This finding presents an alternative, novel explanation for the stress fiber formation and provides new insight into the mechanism of mechanotransduction. Author SummaryRemodeling the cytoskeletal network in response to external force is key to mechanosensing and locomotion. Despite much focus on cytoskeletal remodeling in recent years, a comprehensive understanding of actin remodeling in real-time in cells under mechanical stimuli is still lacking. We integrated stress-induced 3D actin imaging and 3D computational simulations of actin cytoskeleton to study how the actin cytoskeleton form bundles and how these bundles evolve over time upon external tensile stress. We found a rapid actin alignment and a slower bundle evolution leading to denser bundles. Based on these results, we propose a "mechanics before chemistry" model of actin cytoskeleton remodeling under external force.

show abstract

Morphological Transformation and Force Generation of Active Cytoskeletal Networks

Cited by 52 publications

References 38 publications

Crosslinkers both drive and brake cytoskeletal remodeling and furrowing in cytokinesis

Crosslinkers both drive and brake cytoskeletal remodeling and furrowing in cytokinesis

Existing actin filaments orient new filament growth to provide structural memory of filament alignment during cytokinesis

Tensile Force Induced Cytoskeletal Reorganization: Mechanics Before Chemistry

Contact Info

Product

Resources

About