Formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex provides mechanical thrust for membrane fusion, but its molecular mechanism is still unclear. Here using magnetic tweezers, we observe mechanical responses of a single neuronal SNARE complex under constant pulling force. Single SNARE complexes may be unzipped with 34 pN force. When rezipping is induced by lowering the force to 11 pN, only a partially assembled state results, with the C-terminal half of the SNARE complex remaining disassembled. Reassembly of the C-terminal half occurs only when the force is further lowered below 11 pN. Thus, mechanical hysteresis, characterized by the unzipping and rezipping cycle of a single SNARE complex, produces the partially assembled state. In this metastable state, unzipping toward the N-terminus is suppressed while zippering toward the C-terminus is initiated as a steep function of force. This ensures the directionality of SNARE-complex formation, making the SNARE complex a robust force-generating machine.

Magnetic tweezers (MT) are single-molecule manipulation instruments that utilize a magnetic field to apply force to a biomolecule-tethered magnetic bead while using optical bead tracking to measure the biomolecule’s extension. While relatively simple to set up, prior MT implementations have lacked the resolution necessary to observe sub-nanometer biomolecular configuration changes. Here, we demonstrate a reflection-interference technique for bead tracking, and show that it has much better resolution than traditional diffraction-based systems. We enhance the resolution by fabricating optical coatings on all reflecting surfaces that optimize the intensity and contrast of the interference image, and we implement feedback control of the focal position to remove drift. To test the system, we measure the length change of a DNA hairpin as it undergoes a folding/unfolding transition.

Optical vortex trapping can allow the capture and manipulation of micro-and nanometresized objects such as damageable biological particles or particles with a refractive index lower than the surrounding material. However, the quest for nanometric optical vortex trapping that overcomes the diffraction limit remains. Here we demonstrate the fi rst experimental implementation of low-power nano-optical vortex trapping using plasmonic resonance in gold diabolo nanoantennas. The vortex trapping potential was formed with a minimum at 170 nm from the central local maximum, and allowed polystyrene nanoparticles in water to be trapped strongly at the boundary of the nanoantenna. Furthermore, a large radial trapping stiffness, ~ 0.69 pN nm − 1 W − 1 , was measured at the position of the minimum potential, showing good agreement with numerical simulations. This subwavelength-scale nanoantenna system capable of low-power trapping represents a signifi cant step toward versatile, effi cient nano-optical manipulations in lab-on-a-chip devices.

Despite the recent development in the design of DNA origami, its folding yet relies on thermal or chemical annealing methods. We here demonstrate mechanical folding of the DNA origami structure via a pathway that has not been accessible to thermal annealing. Using magnetic tweezers, we stretch a single scaffold DNA with mechanical tension to remove its secondary structures, followed by base pairing of the stretched DNA with staple strands. When the force is subsequently quenched, folding of the DNA nanostructure is completed through displacement between the bound staple strands. Each process in the mechanical folding is well defined and free from kinetic traps, enabling us to complete folding within 10 min. We also demonstrate parallel folding of DNA nanostructures through multiplexed manipulation of the scaffold DNAs. Our results suggest a path towards programmability of the folding pathway of DNA nanostructures.

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease worldwide, but its cause remains unclear. Although a few drugs can provide temporary and partial relief of symptoms in some patients, no curative treatment is available. Therefore, attention has been focused on research using stem cells to treat AD. Among stem cells, mesenchymal stem cells (MSCs) have been used to treat the related pathologies in animal models of AD, and other neurodegenerative disease. This review describes latest research trends on the use of MSC-based therapies in AD and its action of mechanism. MSCs have several beneficial effects. They would be specified as the reduction of neuroinflammation, the elimination of amyloid-β, neurofibrillary tangles, and abnormal protein degradation, the promotion of autophagy-associated and blood-brain barrier recoveries, the upregulation of acetylcholine levels, improved cognition, and the recovery of mitochondrial transport. Therefore, this review describes the latest research trends in MSC-based therapy for AD by demonstrating the importance of MSC-based therapy and understanding of its mechanisms in AD and discusses the limitations and perspectives of stem cell therapy in AD.