5-Methylcytosine (m5C) is one of the most prevalent internal modifications of messenger RNA (mRNA) in higher eukaryotes. Here we report that Y box protein 2 (YBX2) serves as a novel mammalian m5C binding protein to undergo liquid-liquid phase separation (LLPS) both in vivo and in vitro, and this YBX2-dependent LLPS is enhanced by m5C marked RNA. Furthermore, the crystal structure assay revealed that W100, as a distinct m5C binding site of YBX2, is critical in mediating YBX2 phase separation. Our study resolved the relationship between RNA m5C and phase separation, providing a clue for a new regulatory layer of epigenetics.

A single liquid droplet in the air generated by ultrasonic levitation provides such analytical advantages as a small sample volume (~ μL) for expensive proteins, container-free condition for deeply supercooling and supersaturation, time-dependent observation, and homogeneous rapid mixing. The investigation of the properties and structure of a droplet at a molecular level is highly needed for understanding the physicochemical behaviors of a droplet and an underlying mechanism of processes in the droplet. We develop in situ Raman and synchrotron X-ray scattering methods of a single liquid droplet of ~ 1 mm size ultrasonically levitated. The composition of a supersaturated Mg(NO3)2 droplet and speciation in the droplet are determined by analyzing the nitrate N-O and the water O-H stretching vibrational Raman bands. The X-ray interference function of an supersaturated Mg(NO3)2 droplet is subjected to an empirical potential structure refinement modeling to reveal the ion solvation, association, and solvent water structure. Furthermore, crystallization of Mg(NO3)2⋅nH2O from a saturated droplet is observed and identified.

As a major microtubule-associated protein, tau is involved in the assembly of microtubules in the central nervous system. However, under pathological conditions tau assembles into amyloid filaments. Liquid droplets formed by liquid-liquid phase separation (LLPS) are a recently identified assembly state of tau and may have a major effect on the physiological function of tau and the formation of tau aggregates. 14-3-3 proteins are ubiquitously expressed in various tissues and regulate a wide variety of biological processes. In this work, we demonstrate that 14-3-3ζ is recruited into tau droplets and regulates tau LLPS by in vitro assays. While the mobility of tau molecules inside the droplets is not affected in the presence of 14-3-3ζ, the amount and size of droplets can vary significantly. Mechanistic studies reveal that 14-3-3ζ regulates tau LLPS by electrostatic interactions and hydrophobic interactions with the proline-rich domain and the microtubule-binding domain of tau. Surprisingly, the disordered C-terminal tail rather than the amphipathic binding groove of 14-3-3ζ plays a key role. Our findings not only provide a novel dimension to understand the interactions between 14-3-3 proteins and tau, but also suggest that 14-3-3 proteins may play an important role in regulating the LLPS of their binding partners.

Controllable directional transport of liquid droplets on a functionalized surface has been a challenge in the field of microfluidics because it does not require energy supply, and the physical mechanism of such self-driving transport exhibits extraordinary contribution to fundamental understanding of some biological processes and the design of microfluidic apparatus. In this paper, we report a novel design of a surface microstructure that can realize unidirectional self-driving liquid mercury (Hg) droplet transport on a graphene-covered copper (Cu) substrate with a three-dimensional surface microstructure. We have demonstrated that a liquid Hg droplet spontaneously propagates on a grooved Cu substrate covered by a monolayer graphene without any external force fields. Classical molecular dynamics results provide a profound insight on the self-driving process of Hg droplets. It shows that the Hg droplet undergoes acceleration, deceleration, and return stages successively from the narrow to wide ends of the gradient groove. Intriguingly, Hg droplets can move continuously and unidirectionally on the three-dimensional graphene-covered surface microstructure when they accumulate enough kinetic energy from the gradient groove to break the energy barrier at the step junctions between the two neighboring unit cells. The design of the zigzag textured surface covered by a monolayer graphene artfully uses the facts; (1) the monolayer graphene can effectively reduce the droplet pinning on the textured surface, (2) the hydrophobic graphene layer reduces the friction between Hg droplets and the substrate, and (3) the textured surface can permeably interact with the droplets through the monolayer graphene to achieve a continuous self-driving process. The findings reported here open a door to explore the graphene-covered functional surface to directional transport of liquid droplets and provide an in-depth understanding of the self-driving mechanism for liquid droplets on graphene-covered textured substrates.

Herein we report a self-powered multimodal temperature and force sensor based on the reverse electrowetting effect and the thermogalvanic effect in a liquid droplet. The deformation of the droplet and the temperature difference across the droplet can induce an alternating pulse voltage and a direct voltage, respectively, which is easy to separate/analyze and can be utilized to sense the external force and temperature simultaneously. In addition, an integral display system that can derive information from external temperature/force concurrently is constructed. Combined with advantages of excellent sensing properties and a simple structure, the droplet sensor has promising applications in a wide range of intelligent electronics.

Facile manipulation of a tiny liquid droplet is an important but challenging issue for many miniaturized chemical and biological systems. Here we report that a microdroplet can be readily and remotely manipulated in aqueous environments under ambient conditions. The droplet is encapsulated with photothermal nanoparticles to form a liquid marble, and subsequently irradiated with a near-infrared (NIR) laser. The marble is able to ascend, shuttle, horizontally move, and even suspend in water by simply controlling the laser irradiation. Moreover, filling and draining of the marble can also be conducted on the water surface for the first time. This facile manipulation strategy does not use complicated nanostructures or sophisticated equipment, so it has potential applications for channel-free microfluidics, smart microreators, microengines, microrobots, and so on.