Active multistage coarsening of actin networks driven by myosin motors

Abstract

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...

Cell-sized liposomes reveal how actomyosin cortical tension drives shape change

“…2 i and ii and Fig. 4, right bar), consistent with previous observations in bulk networks (22)(23)(24)(25)33). The striking finding is that actin-membrane anchoring governs the outcome of cortex contraction.…”

“…Motors assemble into bipolar filaments of an approximate length of 0.7 μm containing around 100 myosins (24). Actin filaments that contain 1/400 of biotinylated actin monomers carry an average of one biotin link per micrometer and are strongly bound via streptavidin or neutravidin to biotinylated lipids of the liposome membrane.…”

“…These approaches have been successfully used to show that contractility of bulk actomyosin networks depends on the kinetic parameters of the motors (21)(22)(23), as well as on the presence of actin cross-linkers that allow build-up of stress (24,25). A recent study of 2D actomyosin networks attached to flat model biomembranes showed that actin-membrane anchoring also influences cortex contractility (26).…”

Cells as liquid motors: Mechanosensitivity emerges from collective dynamics of actomyosin cortex

“…Consistent with prior computational models (25), this equation shows that the contractile stress σ a gives rise to either the buildup of a contractile tension σ (if clamped boundary conditions allow no strain) or a contractile strain rate σ a =ð2τ α EÞ proportional to α myo =τ myo [if free boundary conditions allow strain but not tension buildup (e.g., in the case of superprecipitation in vitro) (33)] or a combination of these. We then asked whether this simple rheological law for the actomyosin cortex could explain the behavior of cells in our microplate experiments (Fig.…”

“…We find v t = 6:5 ± 1:5 nm/s in the 1D model and 4 nm/s for the 3D model, values that are in agreement with the literature value (18) of 4:3 ± 1:2 nm/s. From the 1D model, we also obtain the relaxation time of the cross-linked actomyosin network, τ α = 1;186 ± 258 s, consistent with elastic-like behavior for frequencies higher than 10 −3 Hz, the contractile characteristic time τ c = 521 ± 57 s, consistent with a 24-min completion of actin superprecipitation (33), and σ a S = ð2:0 ± 0:9Þ · 10 3 nN (SI Text, S3.6). These values fit both the plateau ðv = 0Þ force vs. stiffness experimental results ( Fig.…”