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Concentrated suspensions of swimming microorganisms and other forms of active matter are known to display complex, self-organized spatiotemporal patterns on scales that are large compared with those of the individual motile units. Despite intensive experimental and theoretical study, it has remained unclear the extent to which the hydrodynamic flows generated by swimming cells, rather than purely steric interactions between them, drive the self-organization. Here we use the recent discovery of a spiral-vortex state in confined suspensions of Bacillus subtilis to study this issue in detail. Those experiments showed that if the radius of confinement in a thin cylindrical chamber is below a critical value, the suspension will spontaneously form a steady single-vortex state encircled by a counter-rotating cell boundary layer, with spiral cell orientation within the vortex. Left unclear, however, was the flagellar orientation, and hence the cell swimming direction, within the spiral vortex. Here, using a fast simulation method that captures oriented cell–cell and cell–fluid interactions in a minimal model of discrete particle systems, we predict the striking, counterintuitive result that in the presence of collectively generated fluid motion, the cells within the spiral vortex actually swim upstream against those flows. This prediction is then confirmed by the experiments reported here, which include measurements of flagella bundle orientation and cell tracking in the self-organized state. These results highlight the complex interplay between cell orientation and hydrodynamic flows in concentrated suspensions of microorganisms.

Coordinated polymerization of actin filaments provides force for cell migration, morphogenesis and endocytosis. Capping protein (CP) is a central regulator of actin dynamics in all eukaryotes. It binds to actin filament (F-actin) barbed ends with high affinity and slow dissociation kinetics to prevent filament polymerization and depolymerization. However, in cells, CP displays remarkably rapid dynamics within F-actin networks, but the underlying mechanism remains unclear. Here, we report that the conserved cytoskeletal regulator twinfilin is responsible for CP’s rapid dynamics and specific localization in cells. Depletion of twinfilin led to stable association between CP and cellular F-actin arrays, as well as to its retrograde movement throughout leading-edge lamellipodia. These were accompanied by diminished F-actin turnover rates. In vitro single-filament imaging approaches revealed that twinfilin directly promotes dissociation of CP from filament barbed ends, while enabling subsequent filament depolymerization. These results uncover a bipartite mechanism that controls how actin cytoskeleton-mediated forces are generated in cells. Hakala et al. report that twinfilin dissociates capping proteins from the actin filament barbed ends to promote actin turnover at leading-edge lamellipodia.

Hydrodynamic coupling induces a vortex state in bacterial populations. Microfluidic experiments and modelling now demonstrate that lattices of these vortices can self-organize into patterns characterized by ferro- and antiferromagnetic order. Despite their inherently non-equilibrium nature 1 , living systems can self-organize in highly ordered collective states 2 , 3 that share striking similarities with the thermodynamic equilibrium phases 4 , 5 of conventional condensed-matter and fluid systems. Examples range from the liquid-crystal-like arrangements of bacterial colonies 6 , 7 , microbial suspensions 8 , 9 and tissues 10 to the coherent macro-scale dynamics in schools of fish 11 and flocks of birds 12 . Yet, the generic mathematical principles that govern the emergence of structure in such artificial 13 and biological 6 , 7 , 8 , 9 , 14 systems are elusive. It is not clear when, or even whether, well-established theoretical concepts describing universal thermostatistics of equilibrium systems can capture and classify ordered states of living matter. Here, we connect these two previously disparate regimes: through microfluidic experiments and mathematical modelling, we demonstrate that lattices of hydrodynamically coupled bacterial vortices can spontaneously organize into distinct patterns characterized by ferro- and antiferromagnetic order. The coupling between adjacent vortices can be controlled by tuning the inter-cavity gap widths. The emergence of opposing order regimes is tightly linked to the existence of geometry-induced edge currents 15 , 16 , reminiscent of those in quantum systems 17 , 18 , 19 . Our experimental observations can be rationalized in terms of a generic lattice field theory, suggesting that bacterial spin networks belong to the same universality class as a wide range of equilibrium systems.

The ability of cells to generate forces through actin filament turnover was an early adaptation in evolution. While much is known about how actin filaments grow, mechanisms of their disassembly are incompletely understood. The best-characterized actin disassembly factors are the cofilin family proteins, which increase cytoskeletal dynamics by severing actin filaments. However, the mechanism by which severed actin filaments are recycled back to monomeric form has remained enigmatic. We report that cyclase-associated-protein (CAP) works in synergy with cofilin to accelerate actin filament depolymerization by nearly 100-fold. Structural work uncovers the molecular mechanism by which CAP interacts with actin filament pointed end to destabilize the interface between terminal actin subunits, and subsequently recycles the newly-depolymerized actin monomer for the next round of filament assembly. These findings establish CAP as a molecular machine promoting rapid actin filament depolymerization and monomer recycling, and explain why CAP is critical for actin-dependent processes in all eukaryotes. The cofilin family proteins are actin disassembly factors but the disassembly mechanism is poorly understood. Here authors show that cyclase-associated-protein (CAP) works in synergy with cofilin to accelerate actin filament depolymerization by nearly 100-fold and reveal how CAP destabilizes the interface between terminal actin subunits.

Cytokinetic abscission, the terminal step of cell division, crucially depends on the local constriction of ESCRT-III helices after cytoskeleton disassembly. While the microtubules of the intercellular bridge are cut by the ESCRT-associated enzyme Spastin, the mechanism that clears F-actin at the abscission site is unknown. Here we show that oxidation-mediated depolymerization of actin by the redox enzyme MICAL1 is key for ESCRT-III recruitment and successful abscission. MICAL1 is recruited to the abscission site by the Rab35 GTPase through a direct interaction with a flat three-helix domain found in MICAL1 C terminus. Mechanistically, in vitro assays on single actin filaments demonstrate that MICAL1 is activated by Rab35. Moreover, in our experimental conditions, MICAL1 does not act as a severing enzyme, as initially thought, but instead induces F-actin depolymerization from both ends. Our work reveals an unexpected role for oxidoreduction in triggering local actin depolymerization to control a fundamental step of cell division. Cytokinetic abscission relies on the local constriction after cytoskeleton disassembly, but it is not known how the actin filaments are disassembled. Here, the authors show that the redox enzyme MICAL1 is recruited by Rab35 and induces oxidation-mediated depolymerization of actin, which is required to recruit ESCRT-III and complete abscission.

The prevalence of multicellular organisms is due in part to their ability to form complex structures. How cells pack in these structures is a fundamental biophysical issue, underlying their functional properties. However, much remains unknown about how cell packing geometries arise, and how they are affected by random noise during growth - especially absent developmental programs. Here, we quantify the statistics of cellular neighborhoods of two different multicellular eukaryotes: lab-evolved ‘snowflake’ yeast and the green alga Volvox carteri . We find that despite large differences in cellular organization, the free space associated with individual cells in both organisms closely fits a modified gamma distribution, consistent with maximum entropy predictions originally developed for granular materials. This ‘entropic’ cellular packing ensures a degree of predictability despite noise, facilitating parent-offspring fidelity even in the absence of developmental regulation. Together with simulations of diverse growth morphologies, these results suggest that gamma-distributed cell neighborhood sizes are a general feature of multicellularity, arising from conserved statistics of cellular packing.

The functional importance of the methylation of histidine 73 (H73) in actin remains unclear. Focusing on cytoplasmic β -actin, present in all mammalian cells, we use molecular dynamics simulations with a polarizable force field and adaptive sampling to examine the effects of H73 methylation. Our results show that methylation enhances nucleotide binding cleft opening, alters allosteric pathways connecting subdomains 2 and 4 (SD2 and SD4) in G-actin, and affects backdoor openings and inorganic phosphate release in F-actin, as validated by biochemical assays. These effects depend on the nucleotide and ions interacting with the actin. Together, our findings reveal how H73 methylation regulates β -actin plasticity and integrates environmental cues. Histidine 73 methylation in β -actin modulates actin plasticity, affecting monomer dynamics and filament stability. Using molecular dynamics simulations, the study reveals that methylation influences nucleotide binding cleft opening and phosphate release.

Actin polymerization generates forces for cellular processes throughout the eukaryotic kingdom, but our understanding of the ‘ancient’ actin turnover machineries is limited. We show that, despite > 1 billion years of evolution, pathogenic Leishmania major parasite and mammalian actins share the same overall fold and co-polymerize with each other. Interestingly, Leishmania harbors a simple actin-regulatory machinery that lacks cofilin ‘cofactors’, which accelerate filament disassembly in higher eukaryotes. By applying single-filament biochemistry we discovered that, compared to mammalian proteins, Leishmania actin filaments depolymerize more rapidly from both ends, and are severed > 100-fold more efficiently by cofilin. Our high-resolution cryo-EM structures of Leishmania ADP-, ADP-Pi- and cofilin-actin filaments identify specific features at actin subunit interfaces and cofilin-actin interactions that explain the unusually rapid dynamics of parasite actin filaments. Our findings reveal how divergent parasites achieve rapid actin dynamics using a remarkably simple set of actin-binding proteins, and elucidate evolution of the actin cytoskeleton. The authors report here the structure-function analysis of highly divergent actin from Leishmania parasite. The study reveals remarkably rapid dynamics of parasite actin as well as the underlying molecular basis, thus providing insight into evolution of the actin cytoskeleton.

A Correction to this paper has been published: https://doi.org/10.1038/s41556-021-00651-8.

The regulated assembly of actin filaments is essential in nearly all cell types. Studying actin assembly dynamics can pose many technical challenges. A number of these challenges can be overcome by using microfluidics to observe and manipulate single actin filaments under an optical microscope. In particular, microfluidics can be tremendously useful for applying different mechanical stresses to actin filaments and determining how the physical context of the filaments affects their regulation by biochemical factors. In this review, we summarize the main features of microfluidics for the study of actin assembly dynamics, and we highlight some recent developments that have emerged from the combination of microfluidics and other techniques. We use two case studies to illustrate our points: the rapid assembly of actin filaments by formins and the disassembly of filaments by actin depolymerizing factor (ADF)/cofilin. Both of these protein families play important roles in cells. They regulate actin assembly through complex molecular mechanisms that are sensitive to the filaments’ mechanical context, with multiple activities that need to be quantified separately. Microfluidics-based experiments have been extremely useful for gaining insight into the regulatory actions of these two protein families.