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In many rod-shaped bacteria, the actin homolog MreB directs cell-wall insertion and maintains cell shape, but it remains unclear how structural changes to MreB affect its organization in vivo. Here, we perform molecular dynamics simulations for Caulobacter crescentus MreB to extract mechanical parameters for inputs into a coarse-grained biophysical polymer model that successfully predicts MreB filament properties in vivo. Our analyses indicate that MreB double protofilaments can exhibit left-handed twisting that is dependent on the bound nucleotide and membrane binding; the degree of twisting correlates with the length and orientation of MreB filaments observed in vitro and in vivo. Our molecular dynamics simulations also suggest that membrane binding of MreB double protofilaments induces a stable membrane curvature of similar magnitude to that observed in vivo. Thus, our multiscale modeling correlates cytoskeletal filament size with conformational changes inferred from molecular dynamics simulations, providing a paradigm for connecting protein filament structure and mechanics to cellular organization and function. The actin homolog MreB directs cell-wall insertion and maintains cell shape in many rod-shaped bacteria. Here, Shi et al. perform molecular dynamics simulations for MreB to extract mechanical parameters for inputs into a coarse-grained biophysical polymer model that predicts MreB filament properties.

Swarming is a phenomenon where collective motion arises from simple local interactions between typically identical individuals. Here, we investigate the effects of variability in behavior among the agents in finite swarms with both alignment and cohesive interactions. We show that swarming is abolished above a critical fraction of non-aligners who do not participate in alignment. In certain regimes, however, swarms above the critical threshold can dynamically reorganize and sort out excess non-aligners to maintain the average fraction close to the critical value. This persists even in swarms with a distribution of alignment interactions, suggesting a simple, robust and efficient mechanism that allows heterogeneously mixed populations to naturally regulate their composition and remain in a collective swarming state or even differentiate among behavioral phenotypes. We show that, for evolving swarms, this self-organized sorting behavior can couple to the evolutionary dynamics leading to new evolutionarily stable equilibrium populations set by the physical swarm parameters.

Motor-based transport mechanisms are critical for a wide range of eukaryotic cell functions, including the transport of vesicle cargos over long distances. Our understanding of the factors that control and regulate motors when bound to a lipid substrate is however incomplete. We used microtubule gliding assays on a lipid bilayer substrate to investigate the role of membrane diffusion in kinesin-1 on/off binding kinetics and thereby transport velocity. Fluorescence imaging experiments demonstrate motor clustering on single microtubules due to membrane diffusion in the absence of ATP, followed by rapid ATP-induced dissociation during gliding. Our experimental data combined with analytical modeling show that the on/off binding kinetics of the motors are impacted by diffusion and, as a consequence, both the effective binding and unbinding rates for motors are much lower than the expected bare rates. Our results suggest that motor diffusion in the membrane can play a significant role in transport by impacting motor kinetics and can therefore function as a regulator of intracellular transport dynamics.

We present three-dimensional microshells formed by self-assembly of densely-packed 5 nm gold nanoparticles (AuNPs). Surface functionalization of the AuNPs with custom-designed mesogenic molecules drives the formation of a stable and rigid shell wall, and these unique structures allow encapsulation of cargo that can be contained, virtually leakage-free, over several months. Further, by leveraging the plasmonic response of AuNPs, we can rupture the microshells using optical excitation with ultralow power (<2 mW), controllably and rapidly releasing the encapsulated contents in less than 5 s. The optimal AuNP packing in the wall, moderated by the custom ligands and verified using small angle x-ray spectroscopy, allows us to calculate the heat released in this process, and to simulate the temperature increase originating from the photothermal heating, with great accuracy. Atypically, we find the local heating does not cause a rise of more than 50 °C, which addresses a major shortcoming in plasmon actuated cargo delivery systems. This combination of spectral selectivity, low power requirements, low heat production, and fast release times, along with the versatility in terms of identity of the enclosed cargo, makes these hierarchical microshells suitable for wide-ranging applications, including biological ones.

Active, motor-based cargo transport is important for many cellular functions and cellular development. However, the cell interior is complex and crowded and could have many weak, non-specific interactions with the cargo being transported. To understand how cargo-environment interactions will affect single motor cargo transport and multi-motor cargo transport, we use an artificial quantum dot cargo bound with few (~ 1) to many (~ 5–10) motors allowed to move in a dense microtubule network. We find that kinesin-driven quantum dot cargo is slower than single kinesin-1 motors. Excitingly, there is some recovery of the speed when multiple motors are attached to the cargo. To determine the possible mechanisms of both the slow down and recovery of speed, we have developed a computational model that explicitly incorporates multi-motor cargos interacting non-specifically with nearby microtubules, including, and predominantly with the microtubule on which the cargo is being transported. Our model has recovered the experimentally measured average cargo speed distribution for cargo-motor configurations with few and many motors, implying that numerous, weak, non-specific interactions can slow down cargo transport and multiple motors can reduce these interactions thereby increasing velocity. Graphic abstract

Molecular motors such as kinesin-1 drive active, long-range transport of cargos along microtubules in cells. Thermal diffusion of the cargo can impose a randomly directed, fluctuating mechanical load on the motor carrying the cargo. Recent experiments highlighted a strong asymmetry in the sensitivity of single-kinesin run length to load direction, raising the intriguing possibility that cargo diffusion may non-trivially influence motor run length. To test this possibility, here we employed Monte Carlo-based simulations to evaluate the transport of cargo by a single kinesin. Our simulations included physiologically relevant viscous drag on the cargo and interrogated a large parameter space of cytoplasmic viscosities, cargo sizes, and motor velocities that captures their respective ranges in living cells. We found that cargo diffusion significantly shortens single-kinesin runs. This diffusion-based shortening is countered by viscous drag, leading to an unexpected, non-monotonic variation in run length as viscous drag increases. To our knowledge, this is the first identification of a significant effect of cargo diffusion on motor-based transport. Our study highlights the importance of cargo diffusion and load-detachment kinetics on single-motor functions under physiologically relevant conditions.

Molecular motors are mechanoenzymes that actively drive long-range transport in cells. Thermal diffusion of the cargo can result in mechanical load on the motor carrying the cargo; the direction of this diffusion-based load is not correlated with motor motion. Recent single molecule-based experiments highlighted a strong asymmetric dependence of the run length of the single kinesin-1 motor on load direction, raising the intriguing possibility that thermal diffusion of the cargo may non-trivially influence the run length of the motor carrying the cargo. To test this possibility, here we employed Monte Carlo-based stochastic simulations to evaluate the transport of single-kinesin cargos over a large parameter space of physiologically relevant solution viscosities, cargo sizes, and motor velocities. Our simulations uncovered a previously unexplored, significant shortening effect of cargo diffusion on single-kinesin run length. This effect is non-monotonically influenced by viscous drag force on the cargo, which biases the effect of cargo diffusion toward the hindering direction. The non-monotonic variation of cargo run length with drag force is the direct result of the asymmetric response of kinesin's run length to load direction. Our findings may be important for understanding the diverse characteristics of cargo transport, including run length, observed in living cells.

Mechanical forces generated by myosin II molecular motors drive diverse cellular processes, most notably shape change, division and locomotion. These forces may be transmitted over long range through the cytoskeletal medium - a disordered, viscoelastic network of biopolymers. The resulting cell size scale force chains can in principle mediate mechanical interactions between distant actomyosin units, leading to self-organized structural order in the cell cytoskeleton. To investigate this process, we model the actin cytoskeleton on a percolated fiber lattice network, where fibers are modeled as linear elastic elements that can both bend and stretch, whereas myosin motors exert contractile force dipoles. We quantify the range and heterogeneity of force transmission in these networks in response to a force dipole, showing how these depend on varying bond dilution and fiber bending-to-stretching stiffness ratio. By analyzing clusters of nodes connected to highly strained bonds, as well as the decay rate of strain energy with distance from the force dipole, we show that long-range force transmission is screened out by fiber bending in diluted networks. We further characterize the difference in the propagation of tensile and compressive forces. This leads to a dependence of the mechanical interaction between a pair of force dipoles on their mutual separation and orientation. In more homogeneous networks, the interaction between force dipoles recapitulates the power law dependence on separation distance predicted by continuum elasticity theory, while in diluted networks, the interactions are short-ranged and fluctuate strongly with local network configurations. Altogether, our work suggests that elastic interactions between force dipoles in disordered, fibrous media can act as an organizing principle in biological materials.

Foraging, either solitarily or collectively, is a necessary behavior for survival that is demonstrated by many organisms. Foraging can be collectively optimized by utilizing communication between the organisms. Examples of such communication range from high level strategic foraging by animal groups to rudimentary signaling among unicellular organisms. Here we systematically study the simplest form of communication via long range repulsive interactions between two diffusing Brownian searchers on a one-dimensional lattice. We show that the mean first passage time for either of them to reach a fixed target depends non-monotonically on the range of the interaction and can be optimized for a repulsive range that is comparable to the average spacing between searchers. Our results suggest that even the most rudimentary form of collective searching does in fact lower the search time for the foragers suggesting robust mechanisms for search optimization in cellular communities

We study the nature of the frictional jamming transition within the framework of rigidity percolation theory. Slowly sheared frictional packings are decomposed into rigid clusters and floppy regions with a generalization of the pebble game including frictional contacts. We discover a second-order transition controlled by the emergence of a system-spanning rigid cluster accompanied by a critical cluster size distribution. Rigid clusters also correlate with common measures of rigidity. We contrast this result with frictionless jamming, where the rigid cluster size distribution is noncritical.