Molecular Machine

Machines at a molecular level are in perpetual
Brownian motion even at an ambient temperature. One of
the representative issues of researches on molecular
machines is a development of technology, which can
control Brownian motion. This review presents our efforts
to achieve the first rationally designed molecular brake
systems of threading/dethreading motions, a shuttling
motion, and a rocking motion that work reversibly and
quantitatively in response to external stimuli without producing
any chemical wastes. These molecular brake systems
were constructed from a dumbbell shaped secondary
ammonium axle and a ring component having photo and
thermally reactive moiety.

Molecular machines may resolve three distinct bottlenecks of scientific advancement. Nanofactories (Phoenix, 2003) composed of MM may produce atomically perfect products spending negligible amount of energy (Hess, 2004) thus alleviating the energy crisis. Computers made by MM operating thousands of bits at a time may match biological processors mimicking creativity and intelligence (Hall, 2007), thus far considered as the prerogative of nature. State-of-the-art brain surgeries are not yet fatal-less, MMs guided by a nano-brain may execute perfect bloodless surgery (Freitas, 2005). Even though all three bottlenecks converge to a single necessity of nano-brain, futurists and molecular engineers have remained silent on this issue. Our recent invention of 16 bit parallel processor is a first step in this direction (Bandyopadhyay, 2008). However, the device operates inside ultra-high vacuum chamber. For practical application, one needs to design a 3 D standalone architecture. Here, we identify the minimum nano-brain functions for practical applications and try to increase the size from 2 nm to 20 micro-m.

La (re)découverte des travaux de Gilbert Simondon prend en partie la forme d’une « exégèse polémique » : l’explication et la critique internes d’une œuvre jugée difficile d’accès en raison de sa technicité, de son originalité, mais aussi de son historique de publication complexe et lacunaire et du sentiment d’incomplétude suscité par les tensions internes non résolues qu’elle recèle. Depuis notre thèse, nous avons adopté une posture différente : non pas d’exégète, mais d’usager. Il s’y agissait en effet de penser avec Simondon (entre autres) la signification du concept de "technologie" dans les nanotechnologies. Mobiliser les concepts de Simondon nous permettait de faire retour sur les enquêtes de terrains effectuées  pour élucider le mode d’existence des objets "nano" approchés, et nouer un dialogue "technologique" critique avec les chercheurs. Les dix propositions développées ici visent à illustrer la fécondité d’une telle posture d’"usager de Simondon" sur un sujet technoscientifique contemporain.

Glossary cAMP: cyclic adenosine monophosphate. CAP: catabolite activator protein. F(bridge)-helix and G(trigger)-loop: mobile elements of the RNAP catalytic center (sometimes also called 'bridge helix' and 'trigger loop', respectively). i+1: the substrate binding site in the RNAP catalytic center. P lac : promoter of the lactose operon. ppGpp: guanosine tetraphosphate, the effector of the stringent response. RNAP: RNA polymerase. RPc: RNAP-promoter closed complex. RPitc: RNAP-promoter initial transcribing complex. RPo: RNAP-promoter open complex. aCTD: carboxy-terminal domain of alpha subunit. s1, s2, s3, s4: evolutionarily conserved domains of s 70 . s3-s4 linker: sigma subunit linker element connecting domains s3 and s4. s 54 : sigma N, the sigma factor regulating nitrogen metabolism. s 70 : sigma 70, the housekeeping sigma factor in Escherichia coli.

What would be the utility of such machines? Who knows? I cannot see exactly what would happen, but I can hardly doubt that when we have some control of the arrangement of things on a molecular scale we will get an enormously greater range of possible properties that substances can have, and of the different things we can do.

The recognition that mitochondria and plastids are derived from alphaproteobacterial and cyanobacterial endosymbionts, respectively, was one of the greatest advances in modern evolutionary biology. Researchers have yet however to provide detailed cell biological descriptions of how these once free-living prokaryotes were transformed into intracellular organelles. A key area of study in this realm is elucidating the evolution of the molecular machines that control organelle protein topogenesis. Alcock et al. (Science 2010, 327 [5966]:649-650) suggest that evolutionary innovations that established the mitochondrial protein sorting system were driven by the alphaproteobacterial endosymbiont (an "insiders' perspective"). In contrast, here we argue that evolution of mitochondrial and plastid topogenesis may better be understood as an outcome of selective pressures acting on host cell chromosomes (the "outsiders' view").

The eukaryotic cytoplasmic chaperonin containing TCP-1 (CCT) is a hetero-oligomeric complex that assists the folding of actins, tubulins and other proteins in an ATP-dependent manner. To understand the allosteric transitions that occur during the functional cycle of CCT, we imaged the chaperonin complex in the presence of different ATP concentrations. Labeling by monoclonal antibodies that bind specifically to the CCT␣ and CCT␦ subunits enabled alignment of all the CCT subunits of a given type in different particles. The analysis shows that the apo state of CCT has considerable apparent conformational heterogeneity that decreases with increasing ATP concentration. In contrast with the concerted allosteric switch of GroEL, ATP-induced conformational changes in CCT are found to spread around the ring in a sequential fashion that may facilitate domain-by-domain substrate folding. The approach described here can be used to unravel the allosteric mechanisms of other ring-shaped molecular machines.

This account highlight recent developments in the ®eld of supramolecular tetrathiafulvalene (TTF) chemistry. Progress in synthetic TTF chemistry has enabled the preparation of elaborate molecular systems and architectures. System based on host±guest interactions may act as, for example, sensors or molecular switches. Among these systems mechanically interlocked architectures such as catenanes and rotaxanes are now prime candidates for the construction of arti®cial molecular machines and the fabrication of molecular electronic devices. # : S 0 3 7 9 -6 7 7 9 ( 0 2 ) 0 0 3 7 9 -X

The creation of nanometre-sized structures that exhibit controllable motions and functions is a critical step towards building nanomachines. Recent developments in the field of DNA nanotechnology have begun to address these goals, demonstrating complex static or dynamic nanostructures made of DNA. Here we have designed and constructed a rhombus-shaped DNA origami 'nanoactuator' that uses mechanical linkages to copy distance changes induced on one half ('the driver') to be propagated to the other half ('the mirror'). By combining this nanoactuator with split enhanced green fluorescent protein (eGFP), we have constructed a DNA–protein hybrid nanostructure that demonstrates tunable fluorescent behaviours via long-range allosteric regulation. In addition, the nanoactuator can be used as a sensor that responds to specific stimuli, including changes in buffer composition and the presence of restriction enzymes or specific nucleic acids.

This work describes an innovative medical nanorobot architecture based on important discoveries in nanotechnology, integrated circuit patents, and some publications, directly or indirectly related to one of the most challenging new fields of science: molecular machines. Thus, the architecture described in this paper reflects, and is supported by, some remarkable recent achievements and patents in nanoelectronics, wireless communication and power transmission techniques, nanotubes, lithography, biomedical instrumentation, genetics, and photonics. We also describe how medicine can benefit from the joint development of nanodevices which are derived, and which integrate techniques, from artificial intelligence, nanotechnology, and embedded smart sensors. Teleoperated surgical procedures, early disease diagnosis, and pervasive patient monitoring are some possible applications of nanorobots, reflecting progress along a roadmap for the gradual and practical development of nanorobots. To illustrate the described nanorobot architecture, a computational 3D approach with the application of nanorobots for diabetes is simulated using clinical data. Theoretical and practical analysis of system integration modeling is one important aspect for supporting the rapid development in the emerging field of nanotechnology. This provides useful directions for further research and development of medical nanorobotics and suggests a time frame in which nanorobots may be expected to be available for common utilization in therapeutic and medical procedures.

The photoproperties of main group metal complexes with the electron configurations s2 (e.g. Tl+, Sb3+, Te4+) and so (e.g. T13+, Pb4+) were studied on the basis of a general concept which relates characteristic excited states to typical photophysical and photochemical processes. The photochemistry is dominated by metalcentered sp (s2) and ligand to metal charge transfer (so) excited states which are capable of inducing inter-and intramolecular redox reactions.

This article gives a concise but intensive survey on one of the subfields of natural computing -Molecular Computing. Starting with making a brief revisit to Adleman's pioneering work, this paper will give an overview of selected topics of the field from theory to experiments, while the stress is primarily put on research of theoretical achievements of molecular computing models.

This work describes an innovative medical nanorobot architecture based on important discoveries in nanotechnology, integrated circuit patents, and some publications, directly or indirectly related to one of the most challenging new fields of science: molecular machines. Thus, the architecture described in this paper reflects, and is supported by, some remarkable recent achievements and patents in nanoelectronics, wireless communication and power transmission techniques, nanotubes, lithography, biomedical instrumentation, genetics, and photonics. We also describe how medicine can benefit from the joint development of nanodevices which are derived, and which integrate techniques, from artificial intelligence, nanotechnology, and embedded smart sensors. Teleoperated surgical procedures, early disease diagnosis, and pervasive patient monitoring are some possible applications of nanorobots, reflecting progress along a roadmap for the gradual and practical development of nanorobots. To illustrate the described nanorobot architecture, a computational 3D approach with the application of nanorobots for diabetes is simulated using clinical data. Theoretical and practical analysis of system integration modeling is one important aspect for supporting the rapid development in the emerging field of nanotechnology. This provides useful directions for further research and development of medical nanorobotics and suggests a time frame in which nanorobots may be expected to be available for common utilization in therapeutic and medical procedures.

In the course of the last decade, many dynamic molecular systems, whose movements are controlled externally, have been elaborated. These compounds are generally referred to as "molecular machines". Transition-metal-containing catenanes and rotaxanes are ideally suited to build such systems. In the present article, we will discuss a few examples of molecular machines elaborated and studied in Strasbourg. In the first section, we will discuss an electrochemically driven system consisting of a fast-moving pirouetting rotaxane. The second section will be devoted to a linear rotaxane dimer whose behavior is reminiscent of muscle movement, in the sense that it can stretch and contract. In the rest of this article, the focus will be mostly on light-driven machines consisting of ruthenium(II)-complexed rotaxanes, catenanes, and scorpionates. In the case of rotaxanes and catenanes, the synthetic approach is based on the template effect of an octahedral ruthenium(II) center. Two polydentate ligands are incorporated in an axis or in a ring, affording the precursor to the rotaxane or the catenane, respectively. Ru(diimine) 3 2+ and Ru(terpy)(phen)(L) 2+ (terpy: terpyridine; phen: 1,10-phenanthroline) complexes display the universally used 3 MLCT (metal-to-ligand charge transfer) excited state and another interesting excited state, the 3 LF (ligand field) state, which is strongly dissociative. By taking advantage of this latter state, it has been possible to propose a new family of molecular machines, which are set in motion by populating the dissociative 3 LF state, thus leading to ligand exchange in the coordination sphere of the ruthenium(II) center.

Very recently [Phys. Rev. E 82, 021921 (2010)] a simple mechanism was presented by which a molecule subjected to forced oscillations, out of thermal equilibrium, can maintain quantum entanglement between two of its quantum degrees of freedom. Crucially, entanglement can be maintained even in the presence of very intense noise, so intense that no entanglement is possible when the forced oscillations cease. This mechanism may allow for the presence of non-trivial quantum entanglement in biological systems. Here we significantly enlarge the study of this model. In particular, we show that the persistent generation of dynamic entanglement is not restricted to the bosonic heat bath model, but it can also be observed in other decoherence models, e.g. the spin gas model, and in non-Markovian scenarios. We also show how conformational changes can be used by an elementary machine to generate entanglement even in unfavorable conditions. In biological systems, similar mechanisms could be exploited by more complex molecular machines or motors.

Manipulation of self-assembly processes to construct predesigned supramolecular architectures in a controllable manner is of utmost importance in the field of nanotechnology for the development of application-oriented devices. We here summarize recent progress in the current strategies for the manipulation of thin film assemblies on solid surfaces and at interfaces, as well as in freestanding thin film structures. We also highlight our recent progress including a description of the concept of hand-operating nanotechnology for controlling thin film assemblies at dynamic interfaces. This review is organized into three sections: (i) functionalization and manipulation of solid surfaces to assist molecular self-assembly; (ii) manipulation of freestanding ultrathin films by selfassembly; and (iii) molecular assembly at dynamic interfaces.

Several decades of research in biochemistry and molecular biology have been devoted for studies on isolated enzymes and proteins. Recent high throughput technologies in genomics and proteomics have resulted in avalanche of information about several genes, proteins and enzymes in variety of living systems. Though these efforts have greatly contributed to the detailed understanding of a large number of individual genes and proteins, this explosion of information has simultaneously brought out the limitations of reductionism in understanding complex biological processes. The genes or gene products do not function in isolation in vivo. A delicate and dynamic molecular architecture is required for precision of the chemical reactions associated with "life". In future, a paradigm shift is, therefore, envisaged, in biology leading to exploration of molecular organizations in physical and genomic context, a subtle transition from conventional molecular biology to modular biology. A...

Most eukaryotic proteins exist as large multicomponent assemblies with many subunits, which act in concert to catalyze specific cellular activities. Many of these molecular machines are only present in low amounts in their native hosts, which impede purification from source material. Unraveling their structure and function at high resolution will often depend on heterologous overproduction. Recombinant expression of multiprotein complexes for structural studies can entail considerable, sometimes inhibitory, investment in both labor and materials, in particular if altering and diversifying of the individual subunits are necessary for successful structure determination. Our laboratory has addressed this challenge by developing technologies that streamline the complex production and diversification process. Here, we review several of these developments for recombinant multiprotein complex production using the MultiBac baculovirus/insect cell expression system which we created. We also addressed parallelization and automation of gene assembly for multiprotein complex expression by developing robotic routines for multigene vector generation. In this contribution, we focus on several improvements of baculovirus expression system performance which we introduced: the modifications of the transfer plasmids, the methods for generation of composite multigene baculoviral DNA, and the simplified and standardized expression procedures which we delineated using our MultiBac system.

We set up a scenario for the operation of primordial synthesis machines operating in outer space quasi one dimensional channels, where polymers interact with fixed particles. The scheme allows for polymerization, translocation and translation. We will show that under very general conditions the particle/polymer interaction potential has spatial regularities with an average distance of three between neighboring minima. We present

Artificial molecular machines represent a growing field of nanoscience and nanotechnology. Stimulated by chemical reagents, electricity, or light, artificial molecular machines exhibit precisely controlled motion at the molecular level; with this ability molecular machines have the potential to make significant impacts in numerous engineering applications. Compared with molecular machines powered by chemical or electrical energy, light-driven molecular machines have several advantages: light can be switched much faster, work without producing chemical waste, and be used for dual purposes-inducing (writing) as well as detecting (reading) molecular motions. The following issues are significant for light-driven artificial molecular machines in the following aspects: their chemical structures, motion mechanisms, assembly and characterization on solid-state surfaces. Applications in different fields of nanotechnology such as molecular electronics, nano-electro-mechanical systems (NEMS), nanophotonics, and nanomedicine are envisaged.

Ribosome is a molecular machine that moves on a mRNA track while, simultaneously, polymerizing a protein using the mRNA also as the corresponding template. We define, and analytically calculate, two different measures of the efficiency of this machine. However, we arugue that its performance is evaluated better in terms of the translational fidelity and the speed with which it polymerizes a protein. We define both these quantities and calculate these analytically. Fidelity is a measure of the quality of the products while the total quantity of products synthesized in a given interval depends on the speed of polymerization. We show that for synthesizing a large quantity of proteins, it is not necessary to sacrifice the quality. We also explore the effects of the quality control mechanism on the strength of mechano-chemical coupling. We suggest experiments for testing some of the ideas presented here.

The capture and utilization of light is an exquisitely evolved process. The single-component microbial opsins, although more limited than multicomponent cascades in processing, display unparalleled compactness and speed. Recent advances in understanding microbial opsins have been driven by molecular engineering for optogenetics and by comparative genomics. Here we provide a Primer on these light-activated ion channels and pumps, describe a group of opsins bridging prior categories, and explore the convergence of molecular engineering and genomic discovery for the utilization and understanding of these remarkable molecular machines.

Gears are microfabricated down to diameters of a few micrometres. Natural macromolecular motors, of tens of nanometres in diameter, also show gear effects 1 . At a smaller scale, the random rotation of a single-molecule rotor encaged in a molecular stator has been observed 2 , demonstrating that a single molecule can be rotated with the tip of a scanning tunnelling microscope 3,4 (STM). A self-assembled rack-andpinion molecular machine where the STM tip apex is the rotation axis of the pinion was also tested 5 . Here, we present the mechanics of an intentionally constructed molecule-gear on a Au(111) surface, mounting and centring one hexa-t-butylpyrimidopentaphenylbenzene molecule on one atom axis.

Protein secretion plays a central role in modulating the interactions of bacteria with their environments. This is particularly the case when symbiotic bacteria (whether pathogenic, commensal or mutualistic) are interacting with larger host organisms. In the case of Gram-negative bacteria, secretion requires translocation across the outer as well as the inner membrane, and a diversity of molecular machines have been elaborated for this purpose. A number of secreted proteins are destined to enter the host cell (effectors and toxins), and thus several secretion systems include apparatus to translocate proteins across the plasma membrane of the host also. The Plant-Associated Microbe Gene Ontology (PAMGO) Consortium has been developing standardized terms for describing biological processes and cellular components that play important roles in the interactions of microbes with plant and animal hosts, including the processes of bacterial secretion. Here we survey bacterial secretion systems known to modulate interactions with host organisms and describe Gene Ontology terms useful for describing the components and functions of these systems, and for capturing the similarities among the diverse systems.

We present a panoramic view of the utility of coarse-grained (CG) models to study folding and functions of proteins and RNA. Drawing largely on the methods developed in our group over the last twenty years, we describe a number of key applications ranging from folding of proteins with disulfide bonds to functions of molecular machines. After presenting the theoretical basis that justifies the use of CG models, we explore the biophysical basis for the emergence of a finite number of folds from lattice models. The lattice model simulations of approach to the folded state show that non-native interactions are relevant only early in the folding process -a finding that rationalizes the success of structure-based models that emphasize native interactions. Applications of off-lattice C α and models that explicitly consider side chains (C α -SCM) to folding of β-hairpin and effects of macromolecular crowding are briefly discussed. Successful applications of a new class of off-lattice models, referred to as the Self-Organized Polymer (SOP), intended to probe dynamics in large proteins is illustrated by describing the response of Green Fluorescent Protein (GFP) to mechanical force. The unfolding of GFP, at constant loading rate, occurs by the kinetic partitioning mechanism, involving a bifurcation in the pathways. The utility of the SOP model is further illustrated by applications that clarify the functions of the chaperonin GroEL and motion of the molecular motor kinesin.

The self-assembly of surfactant-like peptides containing 4−10 glycines as the component of the hydrophobic tails and aspartic acids as the hydrophilic heads is described. The peptide monomers form nanotubes and nanovesicles in water at neutral pH. These nanostructures become more polydisperse as the length of the glycine tails increases. These unique structures may serve not only as scaffolds for constructing diverse nanodevices but also as enclosures to encapsulate rudimentary enzymes for studying prebiotic molecular evolution.

A microcantilever, coated with a monolayer of redox-controllable, bistable [3]rotaxane molecules (artificial molecular muscles), undergoes reversible deflections when subjected to alternating oxidizing and reducing electrochemical potentials. The microcantilever devices were prepared by precoating one surface with a gold film and allowing the palindromic [3]rotaxane molecules to adsorb selectively onto one side of the microcantilevers, utilizing thiol-gold chemistry. An electrochemical cell was employed in the experiments, and deflections were monitored both as a function of (i) the scan rate (<20 mV s ؊1 ) and (ii) the time for potential step experiments at oxidizing (>؉0.4 V) and reducing (<؉0.2 V) potentials. The different directions and magnitudes of the deflections for the microcantilevers, which were coated with artificial molecular muscles, were compared with (i) data from nominally bare microcantilevers precoated with gold and (ii) those coated with two types of control compounds, namely, dumbbell molecules to simulate the redox activity of the palindromic bistable [3]rotaxane molecules and inactive 1-dodecanethiol molecules. The comparisons demonstrate that the artificial molecular muscles are responsible for the deflections, which can be repeated over many cycles. The microcantilevers deflect in one direction following oxidation and in the opposite direction upon reduction. The ϳ550 nm deflections were calculated to be commensurate with forces per molecule of ϳ650 pN.

Functional rotaxanes are one of the representative nanoscale molecular machines [2] that have found applications in many areas, including molecular electronics, [3] nano-electromechanical systems (NEMS), [4] photocontrollable smart surfaces, and nanovalves. [6] With the advent of molecular recognition and self-assembly, such molecular compounds can now be obtained efficiently through template-directed synthesis. [7] One common strategy for the formation of [2]rotaxanes involves the clipping of a macrocycle around a preformed dumbbell-shaped template in a [1+1] or [2+2] manner ). While early examples were based on irreversible kinetic pathways [8] and covalent bond formation, recent advances in reversible dynamic covalent chemistry (DCC) [9] have attracted great attention to this field. By virtue of thermodynamically controlled equilibria, DCC has provided highly efficient and versatile synthetic routes in the selection of specific products from a complex system. Among

This paper presents an innovative hardware architecture for medical use of nanorobots proposed as an advanced and precise tool for brain aneurysm instrumentation and diagnosis. The feasibility of the outlined architecture is supported by nanobioelectronics, clinical data, and wireless technologies, as embedded integrated system devices for molecular machine data transmission and control upload. The upcoming therapeutic possibility of using nanorobots for aneurysm treatments is the natural result from some recent developments and trends in nanoelectronics, wireless communication, remote power transmission, quantum dots, nanotubes, SOI, lithography, biomedical instrumentation, genome mapping, and photonics. To illustrate the proposed approach, we applied advanced 3D simulation techniques as a practical choice on methodology for medical nanorobotics architecture and integrated system prototyping.

Circadian clocks are self-sustaining genetically based molecular machines that impose $24 h rhythmicity on physiology and behavior that synchronize these functions with the solar day-night cycle. Circadian clocks in the vertebrate retina optimize retinal function by driving rhythms in gene expression, photoreceptor outer segment membrane turnover, and visual sensitivity. This review focuses on recent progress in understanding how clocks and light control arylalkylamine N-acetyltransferase (AANAT), which is thought to drive the daily rhythm in melatonin production in those retinas that synthesize the neurohormone; AANAT is also thought to detoxify arylalkylamines through N-acetylation. The review will cover evidence that cAMP is a major output of the circadian clock in photoreceptor cells; and recent advances indicating that clocks and clock networks occur in multiple cell types of the retina. r

Studies of the past several decades have provided major insights into the structural organization of biological membranes and mechanisms of many membrane molecular machines. However, the origin (s) of the membrane(s) and membrane proteins remain enigmatic. We discuss different concepts of the origin and early evolution of membranes, with a focus on the evolution of the (im)permeability to charged molecules, such as proteins and nucleic acids, and small ions. Reconstruction of the evolution of F-type and A/V-type membrane ATPases (ATP synthases), which are either proton or sodium-dependent, might help understand not only the origin of membrane bioenergetics, but also of membranes themselves. We argue that evolution of biological membranes occurred as a process of co-evolution of lipid bilayers, membrane proteins and membrane bioenergetics.

The need to engineer novel therapeutics and functional materials is driving the in-silico design of molecular complexes. This paper proposes a method to compute symmetric homo-oligomeric protein complexes when the structure of the replicated protein monomer is known and rigid. The relationship between the structure of a protein and its biological function brings the in-silico determination of protein structures associated with functional states to the forefront of computational biology. While protein complexes, arising from associations of protein monomers, are pervasive in every genome, determination of their structures remains challenging. Given the difficulty in computing structures of a protein monomer, computing arrangements of monomers in a complex is mainly limited to dimers. A growth in the number of protein complexes studied in wet labs is allowing classification of their structures. A recent database shows that most naturally-occurring protein complexes are symmetric homo-oligomers. The method presented here exploits this database to propose structures of symmetric homooligomers that can accommodate spatial replications of a given protein monomer. The method searches the database for documented structures of symmetric homo-oligomers where the replicated monomer has a geometrically-similar structure to that of the input protein monomer. The proposed method is a first step towards the in-silico design of novel protein complexes that upon further refinement and characterization can serve as molecular machines or fundamental units in therapeutics or functional materials.

Although the desirability of developing synthetic molecular machine systems that can function on surfaces is widely recognized, to date the only well-characterized examples of electrochemically switchable rotaxane-based molecular shuttles which can do so are based on the tetracationic viologen macrocycle pioneered by Stoddart. Here, we report on a [2]rotaxane which features succinamide and naphthalene diimide hydrogen-bonding stations for a benzylic amide macrocycle that can shuttle and switch its net position both in solution and in a monolayer. Three oxidation states of the naphthalene diimide unit can be accessed electrochemically in solution, each one with a different binding affinity for the macrocycle and, hence, corresponding to a different distribution of the rings between the two stations in the molecular shuttle. Cyclic voltammetry experiments show the switching to be both reversible and cyclable and allow quantification of the translational isomer ratios (thermodynamics) ...

The diversity in structures and physical properties of lipids provides a wide variety of possible interactions with proteins that affect their assembly, organization, and function either at the surface of or within membranes. Because lipids have no catalytic activity, it has been challenging to define many of their precise functions in vivo in molecular terms. Those processes responsive to lipids are attuned to the native lipid environment for optimal function, but evidence that lipids with similar properties or even detergents can sometimes partially replace the natural lipid environment has led to uncertainty as to the requirement for specific lipids. The development of strains of microorganisms in which membrane lipid composition can be genetically manipulated in viable cells has provided a set of reagents to probe lipid functions. These mutants have uncovered previously unrecognized roles for lipids and provided in vivo verification for putative functions described in vitro. In this review, we summarize how these reagent strains have provided new insight into the function of lipids. The role of specific lipids in membrane protein folding and topological organization is reviewed. The evidence is summarized for the involvement of anionic lipidenriched domains in the organization of amphitropic proteins on the membrane surface into molecular machines involved in DNA replication and cell division. D

Chromatin remodeling complexes are ATP-driven molecular machines that change chromatin structure by translocating nucleosomes along the DNA, evicting nucleosomes, or changing the nucleosomal histone composition. They are highly abundant in the cell and numerous different complexes exist that display distinct activity patterns. Here we review chromatin-associated signals that are recognized by remodelers. It is discussed how these regulate the remodeling reaction via changing the nucleosome substrate/product binding affinity or the catalytic translocation rate. Finally, we address the question of how chromatin remodelers operate in the cell nucleus to find specifically marked nucleosome substrates via a diffusion driven target location mechanism, and estimate the search times of this process. This article is part of a Special Issue entitled:Snf2/Swi2 ATPase structure and function.