Helical Molecular Springs under High Pressure

Although the unique structure of helicenes resembles molecular springs, the effects of pressure on their extension–contraction cycles have rarely been explored. Herein, we investigated the fluorescence of two π-extended [n]helicenes with different helical lengths n, here named [7] and [9], under high pressure in a diamond anvil cell. Based on experimental results and theoretical calculations, the mechanical and fluorescent properties of the molecular springs were found to be influenced not only by the intermolecular packing, but also by the intramolecular π-π interactions between their overlapping helixes. As a more rigid molecular spring, [9] exhibited a more sensitive response of its fluorescence to hydrostatic pressure than [7]. Our results provide new insights into structure-property relationships under high-pressure conditions and verify the potential of helicenes as molecular springs for future applications in molecular machines.

Azo-dye Antibacterial with Nanotube-[SiO2(OH)2]9 System for Drug Delivery Investigation

Azo dye, [SiO2(OH)2]9 molecular ring, and single-walled carbon nanotubes (4,4) SWCNT were considered like an axle, a wheel, and stoppers, respectively. The combination of the azo dye on the [SiO2(OH)2]9 molecular ring with (4,4) SWCNTs may be thought of as a non-covalent system in UV light-isomer- machine. A new molecular motor system that runs like a hinge motion is demonstrated like light-powered molecular hinges. A new molecular motor system that acts as a hinge motion has been demonstrated and introduced as light-moving molecular hinges. By emitting various ultraviolet, visible lights, the [SiO2 (OH)2]9 molecular ring in the system can be reversed with the various dumb-bell size on one side attached halogens and fixing it on the other side of the (4,4) SWCNTs surface, a variety of systems in a wide variety of ultraviolet sensors can be designated to a better model of molecular machines and can be used for drug delivery of some antibiotics that are difficult to administer by straight injection. Molecular machines containing a wide variety of ultraviolet sensors have been designed with the combination of azo derivatives formed by replacing different halogens with hydrogen in the azo dye on the [SiO2(OH)2]9 molecular ring to the (4,4) SWCNTs surface.

Probing allosteric interactions in homo-oligomeric molecular machines using solution NMR spectroscopy

Developments in solution NMR spectroscopy have significantly impacted the biological questions that can now be addressed by this methodology. By means of illustration, we present here a perspective focusing on studies of a number of molecular machines that are critical for cellular homeostasis. The role of NMR in elucidating the structural dynamics of these important molecules is emphasized, focusing specifically on intersubunit allosteric communication in homo-oligomers. In many biophysical studies of oligomers, allostery is inferred by showing that models specifically including intersubunit communication best fit the data of interest. Ideally, however, experimental studies focusing on one subunit of a multisubunit system would be performed as an important complement to the more traditional bulk measurements in which signals from all components are measured simultaneously. Using an approach whereby asymmetric molecules are prepared in concert with NMR experiments focusing on the structural dynamics of individual protomers, we present examples of how intersubunit allostery can be directly observed in high-molecular-weight protein systems. These examples highlight some of the unique roles of solution NMR spectroscopy in studies of complex biomolecules and emphasize the important synergy between NMR and other atomic resolution biophysical methods.

Reconstructing essential active zone functions within a synapse

Active zones are molecular machines that control neurotransmitter release through synaptic vesicle docking and priming, and through coupling of these vesicles to Ca2+ entry. The complexity of active zone machinery has made it challenging to determine which mechanisms drive these roles in release. Here, we induce RIM+ELKS knockout to eliminate active zone scaffolding networks, and then reconstruct each active zone function. Re-expression of RIM1-Zn fingers positioned Munc13 on undocked vesicles and rendered them release-competent. Reconstitution of release-triggering required docking of these vesicles to Ca2+ channels. Fusing RIM1-Zn to CaVbeta4-subunits sufficed to restore docking, priming and release-triggering without reinstating active zone scaffolds. Hence, exocytotic activities of the 80 kDa CaVbeta4-Zn fusion protein bypassed the need for megadalton-sized secretory machines. These data define key mechanisms of active zone function, establish that fusion competence and docking are mechanistically separable, and reveal that active zone scaffolding networks are not required for release.

Proteins — a celebration of consilience

Proteins are the common constituents of all living cells. They are molecular machines that interact with each other as well as with other cell products and carry out a dizzying array of functions with distinction. These interactions follow from their native state structures and therefore understanding sequence-structure relationships is of fundamental importance. What is quite remarkable about proteins is that their understanding necessarily straddles several disciplines. The importance of geometry in defining protein native state structure, the constraints placed on protein behavior by mathematics and physics, the need for proteins to obey the laws of quantum chemistry, and the rich role of evolution and biology all come together in defining protein science. Here we review ideas from the literature and present an interdisciplinary framework that aims to marry ideas from Plato and Darwin and demonstrates an astonishing consilience between disciplines in describing proteins. We discuss the consequences of this framework on protein behavior.

DNA Nanodevices: from Mechanical Motions to Biomedical Applications

: Inspired by molecular machines in nature, artificial nanodevices have been designed to realize various biomedical functions. Self-assembled deoxyribonucleic acid (DNA) nanostructures that feature designed geometries, excellent spatial accuracy, nanoscale addressability and marked biocompatibility provide an attractive candidate for constructing dynamic nanodevices with biomarker-targeting and stimuli-responsiveness for biomedical applications. Here, a summary of typical construction strategies of DNA nanodevices and their operating mechanisms are presented. We also introduced recent advances in employing DNA nanodevices as platforms for biosensing and intelligent drug delivery. Finally, the broad prospects and main challenges of the DNA nanodevices in biomedical applications are discussed.

Pumping Between Phases With a Pulsed-Fuel Molecular Ratchet

The sorption of species from solution into and onto solids, surfaces, crystals, gels and other matrices, underpins the sequestering of waste and pollutants, the recovery of precious metals, heterogeneous catalysis, many forms of chemical and biological analysis and separation science, and numerous other technologies. In such cases the transfer of the substrate between phases tends to proceed spontaneously, in the direction of equilibrium. Molecular ratchet mechanisms, where kinetic gating selectively inhibits or accelerates particular steps in a process, makes it possible to drive dynamic systems out of equilibrium. Here we report on a small-molecule pump immobilised on and near the surface of polymer beads, that uses an energy ratchet mechanism to actively transport substrates from solution onto the beads away from equilibrium. One complete cycle of the pump occurs with each pulse of a chemical fuel, synchronizing the ratchet dynamics so that the immobilised molecular machines all act in unison. Upon addition of the trichloroacetic acid fuel, micrometre-diameter polystyrene beads functionalised with an average of ~8×10exp10 molecular pumps per bead, sequester from solution crown ethers appended with a fluorescent tag. Following consumption of the fuel, the rings are mechanically trapped in a higher energy, out-of-equilibrium, state on the beads and cannot be removed by dilution nor by switching the binding interactions off. This differs from dissipative assembled materials that require a continuous supply of energy to persist. Addition of a second pulse of fuel causes the uptake of more macrocycles, which can be labelled with a different fluorescent tag. This drives the system progressively further away from equilibrium and also confers sequence information on the deposited structure. The polymer-bound substrates (and the stored energy) can subsequently be released back to the bulk on demand, either emptying one compartment at a time or all at once. Non-equilibrium sorption by using immobilised artificial molecular machines to pump substrates from solution onto and into materials, offers potential for the transduction of energy from chemical fuels for the storage and release of energy and information.