Molecular Motor-Induced Instabilities and Cross Linkers Determine Biopolymer Organization

Smith, David M.; Ziebert, Falko; Humphrey, David; Duggan, C.; Steinbeck, Matthias; Zimmermann, Walter; Käs, Josef A.

doi:10.1529/biophysj.106.095919

Cited by 104 publications

(109 citation statements)

References 41 publications

(63 reference statements)

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“…Upon complete ATP consumption (initial ATP, <0.01 mM), our actomyosin networks eventually reached a static steady state consistent with earlier reports (54). The cortex of a living cell, however, is continuously driven out of equilibrium by high concentrations (2-5 mM) of ATP (55).…”

Section: Resultssupporting

confidence: 88%

Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer

Köster

Husain

Iljazi

et al. 2016

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

147

152

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The surface of a living cell provides a platform for receptor signaling, protein sorting, transport, and endocytosis, whose regulation requires the local control of membrane organization. Previous work has revealed a role for dynamic actomyosin in membrane protein and lipid organization, suggesting that the cell surface behaves as an active composite composed of a fluid bilayer and a thin film of active actomyosin. We reconstitute an analogous system in vitro that consists of a fluid lipid bilayer coupled via membrane-associated actinbinding proteins to dynamic actin filaments and myosin motors. Upon complete consumption of ATP, this system settles into distinct phases of actin organization, namely bundled filaments, linked apolar asters, and a lattice of polar asters. These depend on actin concentration, filament length, and actin/myosin ratio. During formation of the polar aster phase, advection of the self-organizing actomyosin network drives transient clustering of actin-associated membrane components. Regeneration of ATP supports a constitutively remodeling actomyosin state, which in turn drives active fluctuations of coupled membrane components, resembling those observed at the cell surface. In a multicomponent membrane bilayer, this remodeling actomyosin layer contributes to changes in the extent and dynamics of phasesegregating domains. These results show how local membrane composition can be driven by active processes arising from actomyosin, highlighting the fundamental basis of the active composite model of the cell surface, and indicate its relevance to the study of membrane organization.T he cell surface mediates interactions between the cell and the outside world by serving as the site for signal transduction. It also facilitates the uptake and release of cargo and supports adhesion to substrates. These diverse roles require that the cell surface components involved in each function are spatially and temporally organized into domains spanning a few nanometers (nanoclusters) to several micrometers (microdomains). The cell surface itself may be considered as a fluid-lipid bilayer wherein proteins are embedded (1). In the living cell, this multicomponent system is supported by an actin cortex, composed of a branched network of actin and a collection of filaments (2-4).Current models of membrane organization fall into three categories: those invoking lipid-lipid and lipid-protein interactions in the plasma membrane [e.g., the fluid mosaic model (1, 5) and the lipid raft hypothesis (6)], or those that appeal to the membrane-associated actin cortex (e.g., the picket fence model) (7), or a combination of these (8, 9). Although these models based on thermodynamic equilibrium principles have successfully explained the organization and dynamics of a range of membrane components and molecules, there is a growing class of phenomena that appears inconsistent with chemical and thermal equilibrium, which might warrant a different explanation. These include aspects of the organization and dynamics of outer leaflet...

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Section: Resultssupporting

confidence: 88%

Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer

Köster

Husain

Iljazi

et al. 2016

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

147

152

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“…At mM ATP concentrations, we did not observe active contractility (Fig. S1D) in line with prior studies (12,13). We attribute this ATP dependence to the low duty ratio of skeletal muscle myosin II.…”

Section: Discussionsupporting

confidence: 92%

“…We attribute this ATP dependence to the low duty ratio of skeletal muscle myosin II. With excess ATP, the duty ratio is only 4%, but lowering the ATP concentration to 100 μM increases the duty ratio about fourfold (12,13,49). In addition to the different ATP level, multiple factors that cause dynamic remodeling in cells are absent in our assay.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to microtubules, purified F-actin does not form well-defined structures when motors are added. Actin-myosin II solutions remain disordered at high levels of ATP (12)(13)(14) and generate dense condensates that appear internally unstructured if the ATP level is lowered or when the actin filaments are cross-linked (15)(16)(17)(18). Interestingly, similar dense condensates appear in cells during myosin-driven shape changes of the actin cytoskeleton.…”

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confidence: 99%

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Active multistage coarsening of actin networks driven by myosin motors

Silva

Depken

Stuhrmann

et al. 2011

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

216

174

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In cells, many vital processes involve myosin-driven motility that actively remodels the actin cytoskeleton and changes cell shape. Here we study how the collective action of myosin motors organizes actin filaments into contractile structures in a simplified model system devoid of biochemical regulation. We show that this self-organization occurs through an active multistage coarsening process. First, motors form dense foci by moving along the actin network structure followed by coalescence. Then the foci accumulate actin filaments in a shell around them. These actomyosin condensates eventually cluster due to motor-driven coalescence. We propose that the physical origin of this multistage aggregation is the highly asymmetric load response of actin filaments: they can support large tensions but buckle easily under piconewton compressive loads. Because the motor-generated forces well exceed this threshold, buckling is induced on the connected actin network that resists motor-driven filament sliding. We show how this buckling can give rise to the accumulation of actin shells around myosin foci and subsequent coalescence of foci into superaggregates. This new physical mechanism provides an explanation for the formation and contractile dynamics of disordered condensed actomyosin states observed in vivo.active gels | molecular motors | nonequilibrium | soft condensed matter C ells undergo dramatic changes in shape and internal organization during vital processes such as migration and division. These changes involve remodeling of the cytoskeleton partly driven by collective physical interactions between molecular motors and cytoskeletal filaments. The motors use adenosine triphosphate (ATP) as fuel and hydrolyze it to actively generate forces and move along filaments (1). Multiheaded motors or complexes of motors may cross-link neighboring filaments and generate relative motion between them. Kinesin and dynein motors interact with microtubules to form the mitotic spindle, which is responsible for chromosome segregation (2). Myosin motors interact with filamentous actin (F-actin) to form complex arrays such as the contractile ring driving cell division (3, 4) and contractile networks that drive cell migration (4) and polarizing cortical flows (5, 6).To identify the biophysical processes underlying cytoskeletal organization, many in vitro model systems of purified motors and filaments that lack biochemical regulation have been recently developed. It is known that kinesins can organize microtubules into polarity sorted asters, as well as vortex or bundle states (7-10). These structures resemble physiological arrays such as the mitotic spindle (11). In contrast to microtubules, purified F-actin does not form well-defined structures when motors are added. Actin-myosin II solutions remain disordered at high levels of ATP (12-14) and generate dense condensates that appear internally unstructured if the ATP level is lowered or when the actin filaments are cross-linked (15-18). Interestingly, similar dense condensates appear in...

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“…Some examples include the formation of the cytoskeleton [15] and the assembly of mitotic spindles, which are used by eukaryotic cells to segregate chromosomes during cell division [17]. In each of these instances, microtubules undergo motor mediated attachment, cross-linking, and sliding which ultimately leads to the formation of highly organized structures [35]. The dynamics and self-organization of the cytoskeleton [27] is an important subject of study in the biological sciences as well as in soft matter physics as a natural realization of an out-of-equilibrium, complex fluid.…”

Section: Introductionmentioning

confidence: 99%

Motor-Mediated Microtubule Self-Organization in Dilute and Semi-Dilute Filament Solutions

Swaminathan

Ziebert

Aranson

et al. 2010

Math. Model. Nat. Phenom.

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Abstract. We study molecular motor-induced microtubule self-organization in dilute and semidilute filament solutions. In the dilute case, we use a probabilistic model of microtubule interaction via molecular motors to investigate microtubule bundle dynamics. Microtubules are modeled as polar rods interacting through fully inelastic, binary collisions. Our model indicates that initially disordered systems of interacting rods exhibit an orientational instability resulting in spontaneous ordering. We study the existence and dynamic interaction of microtubule bundles analytically and numerically. Our results reveal a long term attraction and coalescing of bundles indicating a clear coarsening in the system; microtubule bundles concentrate into fewer orientations on a slow logarithmic time scale. In semi-dilute filament solutions, multiple motors can bind a filament to several others and, for a critical motor density, induce a transition to an ordered phase with a nonzero mean orientation. Motors attach to a pair of filaments and walk along the pair bringing them into closer alignment. We develop a spatially homogenous, mean-field theory that explicitly accounts for a force-dependent detachment rate of motors, which in turn affects the mean and the fluctuations of the net force acting on a filament. We show that the transition to the oriented state can be both continuous and discontinuous when the force-dependent detachment of motors is important.

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Molecular Motor-Induced Instabilities and Cross Linkers Determine Biopolymer Organization

Cited by 104 publications

References 41 publications

Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer

Actomyosin dynamics drive local membrane component organization in an in vitro active composite layer

Active multistage coarsening of actin networks driven by myosin motors

Motor-Mediated Microtubule Self-Organization in Dilute and Semi-Dilute Filament Solutions

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