Inner-arm dynein c of Chlamydomonas flagella is a single-headed processive motor.

Axonemal dyneins are force-generating ATPases that produce movement of eukaryotic cilia and flagella. Several studies indicate that inner-arm dyneins mainly produce bending moments in flagella and that these motors have inherent oscillations in force and motility. Processive motors such as kinesins have high duty ratios of attached to total ATPase cycle (attached plus detached) times compared to sliding motors such as myosin. Here we provide evidence that subspecies-c, a single-headed axonemal inner-arm dynein, is processive but has a low duty ratio. Ultrastructurally it is similar to other dyneins, with a single globular head, long stem and a slender stalk that attaches to microtubules. In vitro studies of microtubules sliding over surfaces coated with subspecies-c at low densities (measured by single-molecule fluorescence) show that a single molecule is sufficient to move a microtubule more than 1 microm at 0.7 microm s(-1). When many motors interact the velocity is 5.1 microm s(-1), fitting a duty ratio of 0.14. Using optical trap nanometry, we show that beads carrying a single subspecies-c motor move processively along the microtubules in 8-nm steps but slip backwards under high loads. These results indicate that dynein subspecies-c functions in a very different way from conventional motor proteins, and has properties that could produce self-oscillation in vivo.     

Myosin VI is an actin-based motor that moves backwards.

Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin family includes motors that move towards either the plus or minus ends of microtubules, all characterized myosin motors move towards the barbed (+) end of actin filaments. Crystal structures of myosin II (refs 3-6) have shown that small movements within the myosin motor core are transmitted through the 'converter domain' to a 'lever arm' consisting of a light-chain-binding helix and associated light chains. The lever arm further amplifies the motions of the converter domain into large directed movements. Here we report that myosin VI, an unconventional myosin, moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound to actin using cryo-electron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Thus, it appears that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement.     

分子马达定向运动的合作机制

分子马达是当前生物学和物理学的前沿课题,其定向运动的动力学机制一直是科学家关注的焦点之一.生物体内的分子马达一般是很多个一起协同工作.相互作用与合作在分子马达集体行为中起了很大作用.本文概述了分子马达合作运动的现象和机制.为进一步阐述合作的意义,本文详细讨论了分子马达必须依靠合作才能实现定向输运的两种情况.第一种,分子马达通过合作,在过阻尼条件下克服不停闪烁的棘齿势,实现了定向运动.第二种,分子马达通过合作,可以将一个方向上输入的驱动能量转化到垂直方向上做功,并产生定向输运.     

Unidirectional rotary motion in a molecular system.

The conversion of energy into controlled motion plays an important role in both man-made devices and biological systems. The principles of operation of conventional motors are well established, but the molecular processes used by 'biological motors' such as muscle fibres, flagella and cilia to convert chemical energy into co-ordinated movement remain poorly understood. Although 'brownian ratchets' are known to permit thermally activated motion in one direction only, the concept of channelling random thermal energy into controlled motion has not yet been extended to the molecular level. Here we describe a molecule that uses chemical energy to activate and bias a thermally induced isomerization reaction, and thereby achieve unidirectional intramolecular rotary motion. The motion consists of a 120 degrees rotation around a single bond connecting a three-bladed subunit to the bulky remainder of the molecule, and unidirectional motion is achieved by reversibly introducing a tether between the two units to energetically favour one of the two possible rotation directions. Although our system does not achieve continuous and fast rotation, the design principles that we have used may prove relevant for a better understanding of biological and synthetic molecular motors producing unidirectional rotary motion.     

A mutant of the motor protein kinesin that moves in both directions on microtubules

Molecular motors move directionally to either the plus or the minus end of microtubules or actin filaments. Kinesin moves towards microtubule plus ends, whereas the kinesin-related Ncd motor moves to the minus ends. The 'neck'--the region between the stalk and motor domain--is required for Ncd to move to microtubule minus ends, but the mechanism underlying directional motor movement is not understood. Here we show that a single amino-acid change in the Ncd neck causes the motor to reverse directions and move with wild-type velocities towards the plus or minus end; thus, the neck is functional but directionality is defective. Mutation of a motor-core residue that touches the neck residue in crystal structures also results in movement in both directions, indicating that directed movement to the minus end requires interactions of the neck and motor core. Low-density laser-trap assays show that a conformational change or working stroke of the Ncd motor is directional and biased towards the minus end, whereas that of the neck mutant occurs in either direction. We conclude that the directional bias of the working stroke is dependent on neck/motor core interactions. Absence of these interactions removes directional constraints and permits movement in either direction.     

基于生物群集行为的无人机集群控制

 生物群集行为是一种普遍存在的自然现象,群体中的个体利用简单的规则、局部的交互,形成了鲁棒性强、自适应度高、可扩展性好的自组织行为,在系统层面体现为智能的涌现。本文首先简要叙述了蚁群、蜂群、鸽群、鱼群等典型的生物群集,并从组织结构的分布式、行为主体的简单性、作用模式的灵活性、系统整体的智能性等方面分析了生物群体智能的特点。然后,介绍了部分具有代表性的无人机集群项目,总结了无人机集群的关键技术,包括集群态势感知、自主编队控制、智能协同决策。最后,从生物群集和无人机集群在直观上的相似性出发,分析了生物群体和无人机集群自主控制的映射关系,并探讨了仿生物群集的无人机集群自主控制中的核心问题。     

Quantum dynamics of a single vortex

Vortices occur naturally in a wide range of gases and fluids, from macroscopic to microscopic scales. In Bose-Einstein condensates of dilute atomic gases, superfluid helium and superconductors, the existence of vortices is a consequence of the quantum nature of the system. Quantized vortices of supercurrent are generated by magnetic flux penetrating the material, and play a key role in determining the material properties and the performance of superconductor-based devices. At high temperatures the dynamics of such vortices are essentially classical, while at low temperatures previous experiments have suggested collective quantum dynamics. However, the question of whether vortex tunnelling occurs at low temperatures has been addressed only for large collections of vortices. Here we study the quantum dynamics of an individual vortex in a superconducting Josephson junction. By measuring the statistics of the vortex escape from a controllable pinning potential, we demonstrate the existence of quantized levels of the vortex energy within the trapping potential well and quantum tunnelling of the vortex through the pinning barrier.     

Cytoplasmic dynein functions as a gear in response to load

Cytoskeletal molecular motors belonging to the kinesin and dynein families transport cargos (for example, messenger RNA, endosomes, virus) on polymerized linear structures called microtubules in the cell. These 'nanomachines' use energy obtained from ATP hydrolysis to generate force, and move in a step-like manner on microtubules. Dynein has a complex and fundamentally different structure from other motor families. Thus, understanding dynein's force generation can yield new insight into the architecture and function of nanomachines. Here, we use an optical trap to quantify motion of polystyrene beads driven along microtubules by single cytoplasmic dynein motors. Under no load, dynein moves predominantly with a mixture of 24-nm and 32-nm steps. When moving against load applied by an optical trap, dynein can decrease step size to 8 nm and produce force up to 1.1 pN. This correlation between step size and force production is consistent with a molecular gear mechanism. The ability to take smaller but more powerful strokes under load--that is, to shift gears--depends on the availability of ATP. We propose a model whereby the gear is downshifted through load-induced binding of ATP at secondary sites in the dynein head.     

A microtubule-binding myosin required for nuclear anchoring and spindle assembly

Proper spindle positioning and orientation are essential for asymmetric cell division and require microtubule-actin filament (F-actin) interactions in many systems. Such interactions are particularly important in meiosis, where they mediate nuclear anchoring, as well as meiotic spindle assembly and rotation, two processes required for asymmetric cell division. Myosin-10 proteins are phosphoinositide-binding, actin-based motors that contain carboxy-terminal MyTH4 and FERM domains of unknown function. Here we show that Xenopus laevis myosin-10 (Myo10) associates with microtubules in vitro and in vivo, and is concentrated at the point where the meiotic spindle contacts the F-actin-rich cortex. Microtubule association is mediated by the MyTH4-FERM domains, which bind directly to purified microtubules. Disruption of Myo10 function disrupts nuclear anchoring, spindle assembly and spindle-F-actin association. Thus, this myosin has a novel and critically important role during meiosis in integrating the F-actin and microtubule cytoskeletons.     

Coalignment of vimentin intermediate filaments with microtubules depends on kinesin.

Intermediate filaments in most types of cultured cells coalign with microtubules. Depolymerization of microtubules results in collapse of vimentin and desmin intermediate filaments to the nucleus where they form a perinuclear cap. Collapse can also be induced by microinjection of antibodies against intermediate filament or microtubule proteins. Thus, two filament systems interact with each other. But the molecules mediating this interaction are unknown. One of the candidates for this role is a microtubule motor kinesin. Recent data showed that kinesin is involved in the plus end-directed movement of the membranous organelles along microtubules such as radial extension of lysosomes in macrophages and centrifugal movement of pigment in melanophores. Here we report that injection of the anti-kinesin antibody into human fibroblasts results in the redistribution of intermediate filaments to a tight perinuclear aggregate but had no effect on the distribution of microtubules. Thus, kinesin is involved not only in organelle movement but also in interaction of the two major cytoskeletal systems, intermediate filaments and microtubules.     

A structural change in the kinesin motor protein that drives motility

Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer.     

随机中心耦合布朗马达的定向输运与随机共振

在一些物理和生物环境中,耦合布朗粒子因受介质的温度、浓度等的影响而与周围粒子作用,产生不同程度的粘附和脱落过程,其中便伴随着关联结构的随机解耦合和再耦合行为.本文基于Langevin方程引入了一种新的具有中心随机耦合结构的布朗马达模型来刻画系统输运过程中环境粒子与中心粒子间以一定概率发生局部弹性耦合作用,并形成关联粒子数的随机涨落.仿真结果表明,耦合系统的结构参数、势场对称性及噪声强度等对粒子输运行为均产生显著影响,并且可以观察到系统协作、随机共振和广义随机共振等现象.     

Subatomic movements of a domain wall in the Peierls potential

The discrete nature of crystal lattices plays a role in virtually every material property. But it is only when the size of entities hosted by a crystal becomes comparable to the lattice period--as occurs for dislocations, vortices in superconductors and domain walls--that this discreteness is manifest explicitly. The associated phenomena are usually described in terms of a background Peierls 'atomic washboard' energy potential, which was first introduced for the case of dislocation motion in the 1940s. This concept has subsequently been invoked in many situations to describe certain features in the bulk behaviour of materials, but has to date eluded direct detection and experimental scrutiny at a microscopic level. Here we report observations of the motion of a single magnetic domain wall at the scale of the individual peaks and troughs of the atomic energy landscape. Our experiments reveal that domain walls can become trapped between crystalline planes, and that they propagate by distinct jumps that match the lattice periodicity. The jumps between valleys are found to involve unusual dynamics that shed light on the microscopic processes underlying domain-wall propagation. Such observations offer a means for probing experimentally the physics of topological defects in discrete lattices--a field rich in phenomena that have been subject to extensive theoretical study.     

Switch-based mechanism of kinesin motors

Kinesin motors are specialized enzymes that use hydrolysis of ATP to generate force and movement along their cellular tracks, the microtubules. Although numerous biochemical and biophysical studies have accumulated much data that link microtubule-assisted ATP hydrolysis to kinesin motion, the structural view of kinesin movement remains unclear. This study of the monomeric kinesin motor KIF1A combines X-ray crystallography and cryo-electron microscopy, and allows analysis of force-generating conformational changes at atomic resolution. The motor is revealed in its two functionally critical states-complexed with ADP and with a non-hydrolysable analogue of ATP. The conformational change observed between the ADP-bound and the ATP-like structures of the KIF1A catalytic core is modular, extends to all kinesins and is similar to the conformational change used by myosin motors and G proteins. Docking of the ADP-bound and ATP-like crystallographic models of KIF1A into the corresponding cryo-electron microscopy maps suggests a rationale for the plus-end directional bias associated with the kinesin catalytic core.     

Force generation of organelle transport measured in vivo by an infrared laser trap

Organelle transport along microtubules is believed to be mediated by organelle-associated force-generating molecules. Two classes of microtubule-based organelle motors have been identified: kinesin and cytoplasmic dynein. To correlate the mechanochemical basis of force generation with the in vivo behaviour of organelles, it is important to quantify the force needed to propel an organelle along microtubules and to determine the force generated by a single motor molecule. Measurements of force generation are possible under selected conditions in vitro, but are much more difficult using intact or reactivated cells. Here we combine a useful model system for the study of organelle transport, the giant amoeba Reticulomyxa, with a novel technique for the non-invasive manipulation of and force application to subcellular components, which is based on a gradient-force optical trap, also referred to as 'optical tweezers'. We demonstrate the feasibility of using controlled manipulation of actively translocating organelles to measure direct force. We have determined the force driving a single organelle along microtubules, allowing us to estimate the force generated by a single motor to be 2.6 x 10(-7) dynes.     

Weak pairwise correlations imply strongly correlated network states in a neural population

Biological networks have so many possible states that exhaustive sampling is impossible. Successful analysis thus depends on simplifying hypotheses, but experiments on many systems hint that complicated, higher-order interactions among large groups of elements have an important role. Here we show, in the vertebrate retina, that weak correlations between pairs of neurons coexist with strongly collective behaviour in the responses of ten or more neurons. We find that this collective behaviour is described quantitatively by models that capture the observed pairwise correlations but assume no higher-order interactions. These maximum entropy models are equivalent to Ising models, and predict that larger networks are completely dominated by correlation effects. This suggests that the neural code has associative or error-correcting properties, and we provide preliminary evidence for such behaviour. As a first test for the generality of these ideas, we show that similar results are obtained from networks of cultured cortical neurons.     

基于硬注意力机制下的鱼群涌现自动建模方法

生物集群的协同智能可用于启发人工复杂系统调控,但是现有的自动建模方法往往不符合生物集群信息的处理特点,导致单体的信息交互建模仍充满挑战。不失一般性,借助红鼻剪刀鱼的集群运动数据设计符合生物硬注意力机制的深度网络模型,该结构能强制单体考虑至多两个以内的邻居信息,并能显现出高影响力邻居经常出没的隐藏位置,说明硬注意力模型符合生物集群的信息处理机制。实验结果表明：所提硬注意力模型具有较为良好的稀疏信息解耦能力、较为鲁棒的集群运动指标以及较为优秀的集群规模泛化性能,为复杂系统的多层次行为分析提供了有力的工具支撑,该方法对集群机器人的分布式控制具有较强的启发意义。     

Actin-dependent organelle movement in squid axoplasm.

Studies of organelle movement in axoplasm extruded from the squid giant axon have led to the basic discoveries of microtubule-dependent organelle motility and the characterization of the microtubule-based motor proteins kinesin and cytoplasmic dynein. Rapid organelle movement in higher animal cells, especially in neurons, is considered to be microtubule-based. The role of actin filaments, which are also abundant in axonal cytoplasm, has remained unclear. The inhibition of organelle movement in axoplasm by actin-binding proteins such as DNase I, gelsolin and synapsin I has been attributed to their ability to disorganize the microtubule domains where most of the actin-filaments are located. Here we provide evidence of a new type of organelle movement in squid axoplasm which is independent of both microtubules and microtubule-based motors. This movement is ATP-dependent, unidirectional, actin-dependent, and probably generated by a myosin-like motor. These results demonstrate that an actomyosin-like mechanism can be directly involved in the generation of rapid organelle transport in nerve cells.     

Single kinesin molecules studied with a molecular force clamp.

Kinesin is a two-headed, ATP-driven motor protein that moves processively along microtubules in discrete steps of 8 nm, probably by advancing each of its heads alternately in sequence. Molecular details of how the chemical energy stored in ATP is coupled to mechanical displacement remain obscure. To shed light on this question, a force clamp was constructed, based on a feedback-driven optical trap capable of maintaining constant loads on single kinesin motors. The instrument provides unprecedented resolution of molecular motion and permits mechanochemical studies under controlled external loads. Analysis of records of kinesin motion under variable ATP concentrations and loads revealed several new features. First, kinesin stepping appears to be tightly coupled to ATP hydrolysis over a wide range of forces, with a single hydrolysis per 8-nm mechanical advance. Second, the kinesin stall force depends on the ATP concentration. Third, increased loads reduce the maximum velocity as expected, but also raise the apparent Michaelis-Menten constant. The kinesin cycle therefore contains at least one load-dependent transition affecting the rate at which ATP molecules bind and subsequently commit to hydrolysis. It is likely that at least one other load-dependent rate exists, affecting turnover number. Together, these findings will necessitate revisions to our understanding of how kinesin motors function.     

考虑黏性及压缩效应的旋涡运动特性

采用扩散速度法处理黏性作用项的离散涡法,数值模拟了旋涡在黏性不可压流场中的运动;推导了可压缩流中的旋涡运动方程,对不可压缩流中的Biot-Savart方程进行了可压缩修正,进而用离散涡方法求解出非定常、不稳定、可压缩流场中的旋涡运动。分析了胀量及黏性扩散作用对旋涡运动的影响,通过大量长时间行为的数值试验得出了一系列结果。结果表明：为了真实地反映旋涡在实际流体中的运动规律,必须考虑黏性及压缩性的影响。