Sensing the shape of a surface by intracellular filaments.

Unlabelled: Understanding the mechanisms that dictate the localization of cytoskeletal filaments is crucial for elucidating cell shape regulation in prokaryotes. The actin homolog MreB plays a pivotal role in maintaining the shape of many rod-shaped bacteria such as by directing cell-wall synthesis according to local curvature cues. However, the basis of MreB's curvature-dependent localization has remained elusive.

Migration and proliferation drive the emergence of patterns in co-cultures of differentiating vascular progenitor cells.

Vascular cells self-organize into unique structures guided by cell proliferation, migration, and/or differentiation from neighboring cells, mechanical factors, and/or soluble signals. However, the relative contribution of each of these factors remains unclear. Our objective was to develop a computational model to explore the different factors affecting the emerging micropatterns in 2D.

Tunable intracellular transport on converging microtubule morphologies.

A common type of cytoskeletal morphology involves multiple microtubules converging with their minus ends at the microtubule organizing center (MTOC). The cargo-motor complex will experience ballistic transport when bound to microtubules or diffusive transport when unbound. This machinery allows for sequestering and subsequent dispersal of dynein-transported cargo.

Beyond the kill: The allometry of predation behaviours among large carnivores.

The costs of foraging can be high while also carrying significant risks, especially for consumers feeding at the top of the food chain. To mitigate these risks, many predators supplement active hunting with scavenging and kleptoparasitic behaviours, in some cases specializing in these alternative modes of predation. The factors that drive differential utilization of these tactics from species to species are not well understood.

Synthesis, insertion, and characterization of SARS-CoV-2 membrane protein within lipid bilayers.

Throughout history, coronaviruses have posed challenges to both public health and the global economy; nevertheless, methods to combat them remain rudimentary, primarily due to the absence of experiments to understand the function of various viral components. Among these, membrane (M) proteins are one of the most elusive because of their small size and challenges with expression. Here, we report the development of an expression system to produce tens to hundreds of milligrams of M protein per liter of culture.

Non-specific cargo-filament interactions slow down motor-driven transport.

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.

Effects of cytoskeletal network mesh size on cargo transport.

Intracellular transport of cargoes in the cell is essential for the organization and functioning cells, especially those that are large and elongated. The cytoskeletal networks inside large cells can be highly complex, and this cytoskeletal organization can have impacts on the distance and trajectories of travel. Here, we experimentally created microtubule networks with varying mesh sizes and examined the ability of kinesin-driven quantum dot cargoes to traverse the network.

Optimal mechanical interactions direct multicellular network formation on elastic substrates.

Cells self-organize into functional, ordered structures during tissue morphogenesis, a process that is evocative of colloidal self-assembly into engineered soft materials. Understanding how intercellular mechanical interactions may drive the formation of ordered and functional multicellular structures is important in developmental biology and tissue engineering. Here, by combining an agent-based model for contractile cells on elastic substrates with endothelial cell culture experiments, we show that substrate deformation-mediated mechanical interactions between cells can cluster and align them into branched networks.

Optimal foraging strategies for mutually avoiding competitors.

Many animals are known to exhibit foraging patterns where the distances they travel in a given direction are drawn from a heavy-tailed Lévy distribution. Previous studies have shown that, under sparse and random resource conditions, solitary non-destructive (with regenerating resources) foragers perform a maximally efficient search with Lévy exponent μ equal to 2, while for destructive foragers, efficiency decreases with μ monotonically and there is no optimal μ. However, in nature, there also exist situations where multiple foragers, displaying avoidance behavior, interact with each other competitively.

Feedback linking cell envelope stiffness, curvature, and synthesis enables robust rod-shaped bacterial growth.

Bacterial growth is remarkably robust to environmental fluctuations, yet the mechanisms of growth-rate homeostasis are poorly understood. Here, we combine theory and experiment to infer mechanisms by which adapts its growth rate in response to changes in osmolarity, a fundamental physicochemical property of the environment. The central tenet of our theoretical model is that cell-envelope expansion is only sensitive to local information, such as enzyme concentrations, cell-envelope curvature, and mechanical strain in the envelope.

Cargo surface fluidity can reduce inter-motor mechanical interference, promote load-sharing and enhance processivity in teams of molecular motors.

In cells, multiple molecular motors work together as teams to carry cargoes such as vesicles and organelles over long distances to their destinations by stepping along a network of cytoskeletal filaments. How motors that typically mechanically interfere with each other, work together as teams is unclear. Here we explored the possibility that purely physical mechanisms, such as cargo surface fluidity, may potentially enhance teamwork, both at the single motor and cargo level.

Tuning three-dimensional nano-assembly in the mesoscale via bis(imino)pyridine molecular functionalization.

We investigate the effect of bis(imino)pyridine (BIP) ligands in guiding self-assembly of semiconducting CdSe/ZnS quantum dots (QDs) into three-dimensional multi-layered shells with diameters spanning the entire mesoscopic range, from 200 nm to 2 μm. The assembly process is directed by guest-host interactions between the BIP ligands and a thermotropic liquid crystal (LC), with the latter's phase transition driving the process. Characterization of the shell structures, through scanning electron microscopy and dynamic light scattering, demonstrates that the average shell diameter depends on the BIP structure, and that changing one functional group in the chemical scaffold allows systematic tuning of shell sizes across the entire range.

Active nematic order and dynamic lane formation of microtubules driven by membrane-bound diffusing motors.

Dynamic lane formation and long-range active nematic alignment are reported using a geometry in which kinesin motors are directly coupled to a lipid bilayer, allowing for in-plane motor diffusion during microtubule gliding. We use fluorescence microscopy to image protein distributions in and below the dense two-dimensional microtubule layer, revealing evidence of diffusion-enabled kinesin restructuring within the fluid membrane substrate as microtubules collectively glide above. We find that the lipid membrane acts to promote filament-filament alignment within the gliding layer, enhancing the formation of a globally aligned active nematic state.

Entropy-driven translocation of disordered proteins through the Gram-positive bacterial cell wall.

In Gram-positive bacteria, a thick cross-linked cell wall separates the membrane from the extracellular space. Some surface-exposed proteins, such as the Listeria monocytogenes actin nucleation-promoting factor ActA, remain associated with the bacterial membrane but somehow thread through tens of nanometres of cell wall to expose their amino terminus to the exterior. Here, we report that entropy enables the translocation of disordered transmembrane proteins through the Gram-positive cell wall.

Exploratory dynamics of vocal foraging during infant-caregiver communication.

We investigated the hypothesis that infants search in an acoustic space for vocalisations that elicit adult utterances and vice versa, inspired by research on animal and human foraging. Infant-worn recorders were used to collect day-long audio recordings, and infant speech-related and adult vocalisation onsets and offsets were automatically identified. We examined vocalisation-to-vocalisation steps, focusing on inter-vocalisation time intervals and distances in an acoustic space defined by mean pitch and mean amplitude, measured from the child's perspective.

Chiral twisting in a bacterial cytoskeletal polymer affects filament size and orientation.

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.

Anomalous intracellular transport phases depend on cytoskeletal network features.

Intracellular transport in eukaryotic cells consists of phases of passive, diffusion-based transport and active, motor-driven transport along filaments that make up the cell's cytoskeleton. The interplay between superdiffusive transport along cytoskeletal filaments and the anomalous nature of subdiffusion in the bulk can lead to novel effects in transport behavior at the cellular scale. Here we develop a computational model of the process with cargo being ballistically transported along explicitly modeled cytoskeletal filament networks and passively transported in the cytoplasm by a subdiffusive continuous-time random walk (CTRW).

Membrane mediated motor kinetics in microtubule gliding assays.

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.

Cargo diffusion shortens single-kinesin runs at low viscous drag.

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.

Growth of form in thin elastic structures.

Heterogeneous growth plays an important role in the shape and pattern formation of thin elastic structures ranging from the petals of blooming lilies to the cell walls of growing bacteria. Here we address the stability and regulation of such growth, which we modeled as a quasi-static time evolution of a metric, with fast elastic relaxation of the shape. We consider regulation via coupling of the growth law, defined by the time derivative of the target metric, to purely local properties of the shape, such as the local curvature and stress.

Cell cluster migration: Connecting experiments with physical models.

In multi-cellular organisms, the migration of cohesive clusters of cells containing many individual cells is a common occurrence. Examples include the migration of cells during processes such as the development of the embryo, wound healing, immune response, and the spread of cancer. The migration process depends not only on the traction forces applied by the cluster on its surroundings, in order to move, but also on the viscoelastic properties of both the surrounding matrix and the migrating cellular cluster.

Frustration-induced phases in migrating cell clusters.

Certain malignant cancer cells form clusters in a chemoattractant gradient, which can spontaneously show three different phases of motion: translational, rotational, and random. Guided by our experiments on the motion of two-dimensional clusters in vitro, we developed an agent-based model in which the cells form a cohesive cluster due to attractive and alignment interactions. We find that when cells at the cluster rim are more motile, all three phases of motion coexist, in agreement with our observations.

Interactions between a fluctuating polymer barrier and transport factors together with enzyme action are sufficient for selective and rapid transport through the nuclear pore complex.

The nuclear pore complex, the only pathway for transport between the nucleus and cytoplasm, functions as a highly selective gate that blocks nonspecific macromolecules while allowing the rapid transport of tagged [transport factor (TF) bound] cargo up to an order of magnitude larger. The mechanism of this gate's operation is not yet fully understood and progress has been primarily hindered by the inherent complexity and multiscale nature of the problem. One needs to consider the hundreds of disordered proteins (phenylalanine glycine nucleoporins or FG nups) lining the pore, as well as their overall architecture and dynamics at the microsecond scale, while also accounting for transport at the millisecond scale across the entire pore.

Plasmon-actuated nano-assembled microshells.

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.

Cooperative Interactions between Different Classes of Disordered Proteins Play a Functional Role in the Nuclear Pore Complex of Baker's Yeast.

Nucleocytoplasmic transport is highly selective, efficient, and is regulated by a poorly understood mechanism involving hundreds of disordered FG nucleoporin proteins (FG nups) lining the inside wall of the nuclear pore complex (NPC). Previous research has concluded that FG nups in Baker's yeast (S. cerevisiae) are present in a bimodal distribution, with the "Forest Model" classifying FG nups as either di-block polymer like "trees" or single-block polymer like "shrubs".