Rational engineering of DNA-nanoparticle motor with high speed and processivity comparable to motor proteins

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 16, 2025

DNA-nanoparticle motor is a burnt-bridge Brownian ratchet moving on RNA-modified surface driven by Ribonuclease H (RNase H), and one of the fastest nanoscale artificial motors. However, its speed still much lower than those proteins. Here we resolve elementary processes motion reveal long pauses caused slow RNase binding are bottleneck. As concentration ([RNase H]) increases, pause lengths shorten from ~70 s to ~0.2 s, while step sizes (displacements between two consecutive pauses) constant ( ~ 20 nm). At high [RNase H], reaches ~100 nm s-1, however, processivity (total number steps before detachment), run-length, unidirectionality largely decrease. A geometry-based kinetic simulation reveals switching bottleneck DNA/RNA hybridization at trade-off mechanism other performances. An engineered with 3.8-times larger rate simultaneously achieves 30 s-1 speed, 200 processivity, 3 μm run-length comparable

Язык: Английский

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Structural Influence of the Chemical Fueling System on a Catalysis-Driven Rotary Molecular Motor

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Continuous directionally biased 360° rotation about a covalent single bond was recently realized in the form of chemically fueled 1-phenylpyrrole 2,2′-dicarboxylic acid rotary molecular motor. However, original fueling system and reaction conditions resulted motor directionality only ∼3:1 (i.e., on average backward for every three forward rotations), along with catalytic efficiency operation 97% fuel 14%. Here, we report efficacy series chiral carbodiimide fuels hydrolysis promoters (pyridine pyridine N-oxide derivatives) driving improved directional this motor-molecule. We outline complete network operation, composed directional, futile, slip cycles. Using derivatives where final conformational step is either very slow or completely blocked, phenylpyrrole diacid becomes enantiomerically enriched, allowing kinetic gating individual steps cycle to be measured. The that produces highest gives 13% enantiomeric excess (e.e.) anhydride-forming kinetically gated step, while most effective promoter generates 90% e.e. step. Combining best-performing into results 92% e.e.. Under dilute chemostated regime (to avoid N-acyl urea formation at high concentrations promoters), continuously rotates ∼24:1 24 rotations) >99% 51%.

Язык: Английский

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Anomalous diffusion of active Brownian particles in responsive elastic gels: Nonergodicity, non-Gaussianity, and distributions of trapping times

Physical review. E, Год журнала: 2024, Номер 110(4)

Опубликована: Окт. 29, 2024

Understanding actual transport mechanisms of self-propelled particles (SPPs) in complex elastic gels---such as the cell cytoplasm, vitro networks chromatin or F-actin fibers, mucus gels---has far-reaching consequences. Implications beyond biology/biophysics are engineering and medicine, with a particular focus on microrheology targeted drug delivery. Here, we examine via extensive computer simulations dynamics SPPs deformable gellike structures responsive to thermal fluctuations. We treat tracer comparable larger than mesh size gel. observe distinct trapping events active tracers at relatively short times, leading subdiffusion; it is followed by an escape from meshwork-induced traps due flexibility network, resulting superdiffusion. thus find crossovers between different regimes. also pronounced nonergodicity non-Gaussianity intermediate times. The distributions times escaping ``cages'' our quasiperiodic gel often reveal existence two timescales dynamics. At high activity these become comparable. Furthermore, that mean waiting time exhibits power-law dependence (in terms their P\'eclet number). Our results additionally showcase both exponential nonexponential activities. Extensions this setup possible, factors such anisotropy particles, topologies various interactions (also nonlocal nature) be considered.

Язык: Английский

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On-Demand Photoactivation of DNA-Based Motor Motion

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

A major challenge in the field of synthetic motors relates to mimicking precise, on-demand motion biological motor proteins, which mediates processes such as cargo transport, cell locomotion, and division. To address this challenge, we developed a system control DNA-based using light. DNA are composed central chassis particle modified with "legs" that hybridize RNA "fuel", move upon enzymatic consumption RNA. We first concealed fuel sites photocleavable oligonucleotides block leg binding. Upon UV activation, blocking strands dissociate, exposing initiating active, directional motion. also created "brake" stalling strands, anchoring until light removes while simultaneously "fueling" motors, spatiotemporally controlled stop → go Additionally, activate via chemical input, an optical input is required motors. This dual-input approach, functioning "AND" gate, demonstrates potential for perform light-triggered computational tasks. Our work provides proof concept enhancing complexity functionality

Язык: Английский

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Tumbleweed: an artificial motor protein that walks along a DNA track

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 12, 2025

Abstract Nature has used proteins to evolve molecular motors that facilitate life. Although small-molecule- and DNA-based have been synthesized, the creation of an artificial motor protein remained a goal synthetic biology. Here we describe modular approach create protein, Tumbleweed (TW). TW three legs, each with ligand-gated DNA binding domain controls track. works via Brownian ratchet mechanism where steps are effected by diffusion then rectified controlling ligands. Using single-molecule fluorescence assays microfluidic device, show directionally along track when ligand concentrations altered in sequence.

Язык: Английский

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Kinetic analysis of paramyxovirus-sialoglycan receptor interactions reveals virion motility

PLoS Pathogens, Год журнала: 2023, Номер 19(3), С. e1011273 - e1011273

Опубликована: Март 27, 2023

Many viruses initiate infection by binding to sialoglycan receptors at the cell surface. Binding such comes a cost, however, as sheer abundance of sialoglycans e.g. in mucus, may immobilize virions non-functional decoy receptors. As solution, sialoglycan-binding well sialoglycan-cleavage activities are often present these viruses, which for paramyxoviruses combined hemagglutinin-neuraminidase (HN) protein. The dynamic interactions with their thought be key determinants species tropism, replication and pathogenesis. Here we used biolayer interferometry perform kinetic analyses receptor animal human (Newcastle disease virus, Sendai parainfluenza virus 3). We show that display strikingly different interaction dynamics, correlated receptor-binding -cleavage presence second sialic acid site. Virion was followed sialidase-driven release, during cleaved until virus-specific density reached, largely independent virion concentration. Sialidase-driven release furthermore shown cooperative process affected pH. propose motility on receptor-coated surface, threshold is reached start dissociate. Similar has previously been observed influenza likely also apply sialoglycan-interacting embecoviruses. Analysis balance between increases our understanding host tropism zoonotic potential viruses.

Язык: Английский

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The kinetics and optimality of influenza A virus locomotion

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 9, 2024

Influenza A viruses (IAVs) must navigate through a dense extracellular mucus to infect airway epithelial cells. The mucous layer, composed of glycosylated biopolymers (mucins), presents sialic acid that binds ligands on the viral envelope and can be irreversibly cleaved by enzymes. It was recently discovered filamentous IAVs exhibit directed persistent motion along their long axis acid-coated surfaces. This study demonstrates stochastic simulations mean-field theory, how harness ‘burnt-bridge’ Brownian ratchet mechanism for translational motion. Importantly, our analysis reveals equilibrium features system primarily control dynamics, even out-of-equilibrium, ligand asymmetry allows more robust transport. We show occupy optimal parameter range (‘Goldilocks zone’) efficient transport, possibly due evolutionary adaptation enzyme kinetics. Our findings suggest novel therapeutic targets provide insight into possible mechanisms zoonotic transmission.

Язык: Английский

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Reshaping and Enzymatic Activity may allow Viruses to move through the Mucus

Soft Matter, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Filamentous viruses like influenza and torovirus often display systematic bends arcs of mysterious physical origin. We propose that such undergo an instability from a cylindrically symmetric to toroidally curved state. This "toro-elastic" state emerges

Язык: Английский

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Kinetics and Optimality of Influenza A Virus Locomotion

Physical Review Letters, Год журнала: 2024, Номер 133(24)

Опубликована: Дек. 11, 2024

Influenza A viruses (IAVs) must navigate through a dense extracellular mucus to infect airway epithelial cells. The mucous layer, composed of glycosylated biopolymers (mucins), presents sialic acid that binds ligands on the viral envelope and can be irreversibly cleaved by enzymes. It was recently discovered filamentous IAVs exhibit directed persistent motion along their long axis acid-coated surfaces. This Letter demonstrates stochastic simulations mean-field theory, how harness "burnt-bridge" Brownian ratchet mechanism for translational motion. Importantly, our analysis reveals equilibrium features system primarily control dynamics, even out equilibrium, asymmetric distribution virus allows more robust transport. We show occupy optimal parameter range ("Goldilocks zone") efficient transport, possibly due evolutionary adaptation enzyme kinetics. Our findings suggest novel therapeutic targets provide insight into possible mechanisms zoonotic transmission.

Язык: Английский

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Molecular Lawnmower Drives Itself

Physics, Год журнала: 2024, Номер 17

Опубликована: Март 14, 2024

Язык: Английский

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