Drug Transport Microdevice Mimicking an Idealized Nanoscale Bio-molecular Motor

Molecular motors are nature＇s nano-devices and the essential agents of movement that are an integral part of many living organisms. The supramolecular motor, called Nuclear Pore Complex （NPC）, controls the transport of all cellular material be- tween the cytoplasm and the nucleus that occurs naturally in biological cells of many organisms. In order to understand the design characteristics of the NPC, we developed a microdevice for drug/fluidic transport mimicking the coarse-grained repre- sentation of the NPC geometry through computational fluid dynamic analysis and optimization. Specifically, the role of the central plug in active fluidic/particle transport and passive transport （without central plug） was investigated. Results of flow rate, pressure and velocity profiles obtained from the models indicate that the central plug plays a major role in transport through this biomolecular machine. The results ofthis investigation show that fluidic transport and flow passages are important factors in designing NPC based nano- and micro-devices for drug delivery.

A non-Markov ratchet model of molecular motors：processive movement of single-headed kinesin KIF1A

A fluctuating ratchet model of non-Markov process is presented to describe the processive movement of molecular motors of single-headed kinesin KIF1A, where the fluctuation perturbation to the local potential is introduced and the detailed ATPase pathway of the motor is included. The theoretical results show good quantitative agreement with the previous experimental ones.

A simplified tether model for molecular motor transporting cargo

Molecular motors are proteins or protein complexes which function as transporting engines in biological cells. This paper models the tether between motor and its cargo as a symmetric linear potential. Different from Elston and Peskin＇s work for which performance of the system was discussed only in some limiting cases, this study produces analytic solutions of the problem for general cases by simplifying the transport system into two physical states, which makes it possible to discuss the dynamics of the motor--cargo system in detail. It turns out that the tether strength between motor and cargo should be greater than a threshold or the motor will fail to transport the cargo, which was not discussed by former researchers yet. Value of the threshold depends on the diffusion coefficients of cargo and motor and also on the strength of the Brownian ratchets dragging the system. The threshold approaches a finite constant when the strength of the ratchet tends to infinity.

Periodic thermodynamics of laser-driven molecular motor

Operation of a laser-driven nano-motor inevitably generates a non-trivial amount of heat, which can possibly lead to instability or even hinder the motor＇s continual running. This work quantitatively examines the overheating problem for a recently proposed laser-operated molecular locomotive. We present a single-molecule cooling theory, in which molecular details of the locomotive system are explicitly treated. This theory is able to quantitatively predict cooling efficiency for various candidates of molecular systems for the locomotive, and also suggests concrete strategies for improving the locomotive＇s cooling. It is found that water environment is able to cool the hot locomotive down to room temperature within 100 picoseconds after photon absorption. This cooling time is a few orders of magnitude shorter than the typical time for laser operation, effectively preventing any overheating for the nano-locomotive. However, when the cooling is less effective in non-aqueous environment, residual heat may build up. A continuous running of the motor will then lead to a periodic thermodynamics, which is a common character of many laser-operated nano-devices.

Molecular Motors—Self-Organization of Cytoskeletal Network

Molecular motors play an important role in the organization of cytoskeletal filament networks. These nanometer-sized natural molecular machines opened up a new frontier of nano-technology. This article describes biomolecular nano-machines, their internal structures, and dynamical interactions between molecular motors and their molecular tracks which reorganize a network of long protein filaments, particularly during cell division to form cytoskeleton of daughter cells. Towards the end, the article also takes up some still-to-be resolved matters and prospects for future developments in this exciting multidisciplinary area of science.

Multi-state photoluminescent properties of an overcrowded alkene-based molecular motor in aggregates

Photoisomerization and photoluminescence are two distinct energy dissipation path-ways in light-driven molecular motors.The photoisomerization properties of discrete molecular motors have been well established in solution,but their photoluminescent properties have been rarely reported-especially in aggregates.Here,it is shown that an overcrowded alkene-based molecular motor exhibits distinct dynamic prop-erties in solution and aggregate states,for example,gel and solid states.Despite the poor emissive properties of molecular motors in solution,a bright emission is observed in the aggregate states,including in gel and the crystalline solid.The emis-sion wavelength is highly dependent on the nature of the supramolecular packing and order in the aggregates.As a result,the fluorescent color can be readily tuned reversibly via mechanical grinding and vapor fuming,which provides a new platform for developing multi-stimuli functional materials.

Dynamic Control of Multiple Optical Patterns of Cholesteric Liquid Crystal Microdroplets by Light-Driven Molecular Motors

The key to high-level encryption and anti-counterfeiting techniques is the storage of multiple levels of distinct information that can be individually and precisely addressed by certain stimuli.This continues to be a formidable challenge as the concealed images or codes must be read with fast response and high resolution without cross-talk to the first layer of information.Here,we report a non-fluorescencebased strategy to establish responsive encryption labels taking advantage of solely tuning multiple optical patterns of cholesteric liquid crystal(CLC)microdroplets doped with light-driven molecular motors.The photo-triggered unidirectional rotation of the motor induced not only changes in the helical twist power value but the opposite helical orientation of the superstructure in CLCs as well,resulting in changes in both the structural color and the selective reflection of circularly polar light.The designed labels,which featured highly selective addressability of dual-level distinct information,good reversibility,and viewing angle-independence,were applied to build devices for daily practical use,demonstrating great potential in anti-counterfeiting technology and provide a versatile platform for enhanced data protection and encryption of authentic information.

Collective mechanism of molecular motors and a dynamic mechanical model for sarcomere

A non-equilibrium statistical method is used to study the collective characteristics of myosin II motors in a sarcomere during its contraction. By means of Fokker-Planck equation of molecular motors, we present a dynamic mechanical model for the sarcomere in skeletal muscle. This model has been solved with a numerical algorithm based on experimental chemical transition rates. The influences of ATP concentration and load on probability density, contraction velocity and maximum active force are discussed respectively. It is shown that contraction velocity and maximum isometric active force increase with the increasing ATP concentration and become constant when the ATP concentration reaches equilibrium saturation. Contraction velocity reduces gradually as the load force increases. We also find that active force begins to increase then decrease with the increasing length of sarcomere, and has a maximum value at the optimal length that all myosin motors can attach to actin filament. Our results are in good agreement with the Hill muscle model.

Pharmacologically targeting molecular motor promotes mitochondrial fission for anti-cancer

Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells.Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins.Thus,targeting myosin eactin molecular motor is considered as a promising strategy for anti-cancer.In this study,we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics via pharmacologically targeting molecular motor.Here,we found J13 could directly target myosin-9(MYH9)eactin molecular motor to promote mitochondrial fission progression,and markedly inhibited cancer cells survival,proliferation and migration.Mechanism study revealed that J13 impaired MYH9 eactin interaction to inactivate molecular motor,and caused a cytoskeleton-dependent mitochondrial dynamics imbalance.Moreover,stable isotope labeling with amino acids in cell culture(SILAC)technology-coupled with pulldown analysis identified HSPA9 as a crucial adaptor protein connecting MYH9 eactin molecular motor to mitochondrial fission.Taken together,we reported the first natural small-molecule directly targeting MYH9 eactin molecular motor for anti-cancer translational research.Besides,our study also proved the conceptual practicability of pharmacologically disrupting mitochondrial fission/fusion dynamics in human cancer therapy.

Highly sensitive detection of NT-proBNP by molecular motor

FoF1-ATPase is an active rotary motor,and generates three-ATP for each rotation.At saturated substrate concentration,the motor can achieve about 103 r.p.m,which means one motor can generate about 105 ATP molecules during 30 min.Here,we constituted a novel nanodevice with a molecular rotary motor and a“battery”,FoF1-ATPase and chromatophore,and presented a novel method of sandwich type rotary biosensor based on εsubunit with one target-to-one motor,in which one target corresponds 105 ATP molecules as detection signals during 30 min.The target such as NT-proBNP detection demonstrated that this novel nanodevice has potential to be developed into an ultrasensitive biosensor to detect low expressed targets.

Detectable states, cycle fluxes, and motility scaling of molecular motor kinesin： An integrative kinetic graph theory analysis

The process by which a kinesin motor couples its ATPase activity with concerted mechanical hand- over-hand steps is a foremost topic of molecular motor physics. Two major routes toward elucidating kinesin mechanisms are the motility performance characterization of velocity and run length, and single-molecular state detection experiments. However, these two sets of experimental approaches are largely uncoupled to date. Here, we introduce an integrative motility state analysis based on a theorized kinetic graph theory for kinesin, which, on one hand, is validated by a wealth of accumulated motility data, and, on the other hand, allows for rigorous quantification of state occurrences and chemomechanical cycling probabilities. An interesting linear scaling for kincsin motility performance across species is discussed as well. An integrative kinetic graph theory analysis provides a powerful tool to bridge motility and state characterization experiments, so as to forge a unified effort for the elucidation of the working mechanisms of molecular motors.

Insight into the chemomechanical coupling mechanism of kinesin molecular motors

Kinesin is a two-headed biological molecular motor that can walk processively on microtubule via consumption of ATP molecules.The central issue for the molecular motor is how the chemical energy released from ATP hydrolysis is converted to the kinetic energy of the mechanical motion,namely the mechanism of chemomechanical coupling.To address the issue,diverse experimental methods have been employed and a lot of models have been proposed.This review focuses on the proposed models as well as the qualitative and quantitative comparisons between the results derived from the models and those from the structural,biochemical and single-molecule experimental studies.

Coordinated motion of molecular motors on DNA chains with branch topology

To understand the macroscopic mechanical behaviors of responsive DNA hydrogels integrated with DNA motors,we constructed a state map for the translocation process of a single FtsKc on a single DNA chain at the molecular level and then investigated the movement of single or multiple FtsKc motors on DNA chains with varied branch topologies.Our studies indicate that multiple.FtsKc motors can have coordinated motion,which is mainly due to the force-responsive behavior of individual FtsKc motors.We further suggest the potential application of motors of FtsKc,together with DNA chains of specific branch topology,to serve as strain sensors in hydrogels.

Coordinated motion of molecular motors on DNA chains with branch topology

Toward understanding the macroscopic mechanical behaviors of responsive deoxyribonucleic acid(DNA)hydrogels integrated with DNA motors,here we construct the state map for the translocation process of a single C-terminal translocase domain(FtsKC)on a single DNA chain at the molecular level and then investigate the movement of single or multiple FtsKC motors on DNA chains with varied branch topology.Our studies indicate that multiple FtsKC motors can have coordinated motion,which is mainly due to the force responsive behavior of individual FtsKC motor.We further suggest the potential application of motors of FtsKC,together with DNA chains of specific branch topology,to serve as strain sensors in hydrogels.

Enzyme-free and multiplexed micro RNA detection using micro RNA-initiated DNA molecular motor

In this work,we have developed a sensitive,simple,and enzyme-free assay for detection of micro RNAs(mi RNAs)by means of a DNA molecular motor consisting of two stem-loop DNAs with identical stems and complementary loop domains.In the presence of mi RNA target,it can hybridize with one of the stem-loop DNA to open the stem and to produce a mi RNA/DNA hybrid and a single strand(ss)DNA,the ss DNA will in turn hybridize with another stem-loop DNA and finally form a double strand(ds)DNA to release the mi RNA.One of the stem-loop DNA is double-labeled by a fluorophore/quencher pair with efficiently quenched fluorescence.The formation of ds DNA can produced specific fluorescence signal for mi RNA detection.The released mi RNA will continuously initiate the next hybridization of the two stem-loop DNAs to form a cycle-running DNA molecular motor,which results in great fluorescence amplification.With the efficient signal amplification,as low as 1 pmol/L mi RNA target can be detected and a wide dynamic range from 1 pmol/L to 2 nmol/L is also obtained.Moreover,by designing different stem-loop DNAs specific to different mi RNA targets and labeling them with different fluorophores,multiplexed mi RNAs can be simultaneously detected in one-tube reaction with the synchronous fluorescence spectrum(SFS)technique.

Translating the action of molecular motors to supramolecular polymers

The amplification of asymmetry from the molecular level to the macroscopic scale is an intriguing mechanism operative in natural systems to control complex functions.Inspired by nature,strategies for transferring chiral information across length scales in purely synthetic systems have been investigated.[1,2]Thereof,chiral molecules are embedded into well-defined ordered supramolecular structures with the dynamics of noncovalent interactions leading to the amplification effect.

Coupling mechanism of multi-force interactions in the myosin molecular motor

The dynamics of the myosin molecular motor as it binds to actin filaments during muscle contraction are still not clearly understood.In this paper,we focus on the coupling mechanism of multi-force interactions in the myosin molecule during its interaction with actin.These forces include the electrostatic force,the van der Waals force and the Casimir force in molecular dynamic simulations of the molecules in solvent with thermal fluctuations.Based on the Hamaker approach,van der Waals and Casimir potentials and forces are calculated between myosin and actin.We have developed a Monte Carlo method to simulate the dynamic activity of the molecular motor.We have shown that because of the retardation effect,the van der Waals force falls into the Casimir force when the distance between the surfaces is larger than 3 nm.When the distance is smaller than 3 nm,the electrostatic force and the van der Waals force increase until the myosin becomes attached to the actin.Over the distances studied in the present work,the electrostatic force dominates the attractive interactions.Our calculations are in good agreement with recently reported experimental results.

Biasing fluctuation model for directional stepping motion of molecular motor

The biasing fluctuation model with a colored noise is presented to study the directional stepping motion of the molecular motor. The expression of probability current is obtained in the adiabatic approximation. The force velocity relation and the stepping motion for motor are simulated by Monte Carlo method.

A Theoretical Investigation on Rectifying Performance of a Single Motor Molecular Device

We report ab initio calculations of the transport behavior of a phenyl substituted molecular motor. The calculated results show that the transport behavior of the device is sensitive to the rotation degree of the rotor part. When the rotor part is parallel with the stator part, a better rectifying performance can be found in the current-voltage curve. However, when the rotor part revolves to vertical with the stator part, the currents in the positive bias region decrease slightly. More importantly, the rectifying performance disappears. Thus this offers us a new method to modulate the rectifying behavior in molecular devices.

分子motor定向输运的反常扩散机制

研究了分子motor在非对称闪烁周期势中的反常扩散引起的输运过程 .通过解析和数值方法求解广义Langevin方程 ,得到了粒子稳定定向流 ,研究了其随反常扩散指数δ和无势停留时间τoff的变化规律 .