Gradient Nanoconfinement Facilitates Binding of Transcriptional Factor NF-κB to Histone- and Protamine-DNA Complexes.

Mechanically induced chromosome reorganization plays important roles in transcriptional regulation. However, the interplay between chromosome reorganization and transcription activities is complicated, such that it is difficult to decipher the regulatory effects of intranuclear geometrical cues. Here, we simplify the system by introducing DNA, packaging proteins (i.e., histone and protamine), and transcription factor NF-κB into a well-defined fluidic chip with changing spatical confinement ranging from 100 to 500 nm. It is uncovered that strong nanoconfinement suppresses higher-order folding of histone- and protamine-DNA complexes, the fracture of which exposes buried DNA segments and causes increased quantities of NF-κB binding to the DNA chain. Overall, these results reveal a pathway of how intranuclear geometrical cues alter the open/closed state of a DNA-protein complex and therefore affect transcription activities: i.e., NF-κB binding.

Transpiration-Induced Self-Growth of Texture Hydrogel Surfaces.

Trees grow by coupling the transpiration-induced nutrient absorption from external sources and photosynthesis-based nutrient integration. Inspired by this manner, we designed a class of polyion complex (PIC) hydrogels containing isolated liquid-filled voids for growing texture surfaces. The isolated liquid-filled voids were created via irreversible matrix reconfiguration in a deswelling-swelling process. During transpiration, these voids reversibly collapse to generate negative pressures within the matrices to extract polymerizable compounds from external sources and deliver them to the surface of the samples for photopolymerization. This growth process is spatial-controllable and can be applied to fabricate complex patterns consisting of different compositions, suggesting a new strategy for making texture surfaces.

Escaping Behavior of Sperms on the Biomimetic Oviductal Surface.

Before fertilization, sperms adhere to oviductal epithelium cells, and only a restrictive number of winner sperms can escape to reach the egg. To study the sperm escape behavior from the oviductal surface, we developed a microfluidic chip to fabricate an adhesive surface and to create a gradient of progesterone (P4) for mimicking the oviduct microenvironment in vivo. We identified three sperm motion patterns in such a microenvironment─anchored spin, run-and-spin, and escaped mode. By using kinetic analysis, we verified the hypothesis that the responsive rotation energy anchored with the adhered sperm head determines whether the sperm is trapped or detaching, which is defined as the hammer flying strategy of successful escape after accumulating energy in the process of rotating. Intriguingly, this hammer-throw escaping is able to be triggered by the P4 biochemical stimulation. Our results revealed the tangled process of sperm escape before fertilization in the ingenious microfluidic system.

Swimming of Buoyant Bacteria in Quiescent Medium and Shear Flows.

Gravity has an unavoidable effect on all living organisms inhabiting fluidic surroundings. To investigate the spatial distribution of bacteria in quiescent fluids and their rheotactic behavior in shear flows under buoyancy, we adjust the buoyant force to regulate bacterial swimming in a microfluidic channel. It is found that swimming bacteria of Escherichia coli exhibit an obvious vertical separation when exposed to a medium with high density and gradually gather close to the up wall within minutes. The bacterial population presents a net upward number flux, which enhances the trapping of motile bacteria onto the up surface as a result of buoyancy force apart from the hydrodynamic and kinematic interactions in quiescent fluids. When flow is imposed into the channel, the buoyancy effect is however significantly suppressed. Additionally, the drift velocity perpendicular to the buoyancy vector as a result of chirality-induced transverse swimming decreases with buoyancy force. However, this transverse drift capability is recovered after excluding the intrinsic swimming motility in a quiescent medium. Failing to escape from the trapping as a result of buoyant force allows for a facile separation of bacteria along the vertical direction. The findings also offer a controllable way to redisperse and homogenize the bacteria distribution close to walls by imposing a weak shear flow.

Onset of Nonlinear Electroosmotic Flow under an AC Electric Field.

Nonlinearity of electroosmotic flows (EOFs) is ubiquitous and plays a crucial role in ion transport, specimen mixing, electrochemistry reaction, and electric energy storage and utilization. When and how the transition from a linear regime to a nonlinear one occurs is essential for understanding, prohibiting, or utilizing nonlinear EOF. However, due to the lack of reliable experimental instruments with high spatial and temporal resolutions, the investigation of the onset of nonlinear EOF still remains in theory. Herein, we experimentally studied the velocity fluctuations of EOFs driven by an alternating current (AC) electric field via ultrasensitive fluorescent blinking tricks. The linear and nonlinear AC EOFs are successfully identified from both the time trace and energy spectra of velocity fluctuations. The transitional electric field (EA,C) is determined by both the convection velocity (U) and AC frequency (ff) as EA,C ∼ ff0.48-0.027U. We hope the current investigation could be essential in the development of both theory and applications of nonlinear EOFs.

Drops Sliding on Non-SLIPS Structures.

Inspired by a plant leaf, a slippery liquid-infused porous surface (SLIPS) exhibits attractive nonwetting and self-cleaning abilities. However, rigorous requirements for the infused liquid layer and its inevitable loss limit its practical use. Here, we propose a model structure defined as a non-SLIPS by introducing solid nanostructures covered with a discontinuous lubricant film. This non-SLIPS tuned by solid wettability achieves the excellent self-cleaning feature with a small sliding angle comparable to the counterpart of a typical SLIPS. This sliding angle α* can be further reduced to a saturated plateau by a slight enhancement of hydrophobicity of the solid nanostructures. Interestingly, the sliding velocity remains almost constant for all of these non-SLIPS samples at a given tilt angle, independent of solid wettability. We formulate the slippery mechanism by defining an energy barrier responsible for the sliding initiation on the non-SLIPS. This energy barrier of the non-SLIPS is correlated, with a qualitative agreement, to the molecular adsorption on the solid nanostructures. The antibiological contamination is confirmed for this non-SLIPS, indicating its excellent self-cleaning ability. The findings suggest that the new surfaces, even with the gradual depletion of the infused oil layer, exhibit the nondegradation of the self-cleaning performance.

Ultrasonication-Triggered Ubiquitous Assembly of Magnetic Janus Amphiphilic Nanoparticles in Cancer Theranostic Applications.

The ultrasonication-triggered interfacial assembly approach was developed to synthesize magnetic Janus amphiphilic nanoparticles (MJANPs) for cancer theranostic applications, where the biocompatible octadecylamine is used as a molecular linker to mediate the interactions between hydrophobic and hydrophilic nanoparticles across the oil-water interface. The obtained Co cluster-embedded Fe3O4 nanoparticles-graphene oxide (CCIO-GO) MJANPs exhibited superior magnetic heating efficiency and transverse relaxivity, 64 and 4 times higher than that of commercial superparamagnetic iron oxides, respectively. The methodology has been applicable to nanoparticles of various dimensions (5-100 nm), morphologies (sphere, ring, disk, and rod), and composition (metal oxides, noble metal and semiconductor compounds, etc.), thereby greatly enriching the array of MJANPs. In vivo theranostic applications using the tumor-bearing mice model further demonstrated the effectiveness of these MJANPs in high-resolution multimodality imaging and high-efficiency cancer therapeutics. The ubiquitous assembly approach developed in the current study pave the way for on-demand design of high-performance Janus amphiphilic nanoparticles for various clinical diagnoses and therapeutic applications.

Macroscopic Self-Evolution of Dynamic Hydrogels to Create Hollow Interiors.

A solid-to-hollow evolution in macroscopic structures is challenging in synthetic materials. A fundamentally new strategy is reported for guiding macroscopic, unidirectional shape evolution of materials without compromising the material's integrity. This strategy is based on the creation of a field with a "swelling pole" and a "shrinking pole" to drive polymers to disassemble, migrate, and resettle in the targeted region. This concept is demonstrated using dynamic hydrogels containing anchored acrylic ligands and hydrophobic long alkyl chains. Adding water molecules and ferric ions (Fe3+ ) to induce a swelling-shrinking field transforms the hydrogels from solid to hollow. The strategy is versatile in the generation of various closed hollow objects (for example, spheres, helix tubes, and cubes with different diameters) for different applications.

Label-Free Visualization of Carbapenemase Activity in Living Bacteria.

Evaluating enzyme activity intracellularly on natural substrates is a significant experimental challenge in biomedical research. We report a label-free method for real-time monitoring of the catalytic behavior of class A, B, and D carbapenemases in live bacteria based on measurement of heat changes. By this means, novel biphasic kinetics for class D OXA-48 with imipenem as substrate is revealed, providing a new approach to detect OXA-48-like producers. This in-cell calorimetry approach offers major advantages in the rapid screening (10 min) of carbapenemase-producing Enterobacteriaceae from 142 clinical bacterial isolates, with superior sensitivity (97 %) and excellent specificity (100 %) compared to conventional methods. As a general, label-free method for the study of living cells, this protocol has potential for application to a wider range and variety of cellular components and physiological processes.

Surface roughness induced cracks of the deposition film from drying colloidal suspension.

We investigate crack formation in deposition films from drying colloidal suspension drops, by varying the roughness and texture of the substrate. The experimental results indicate that the crack number or crack spacing presents a general dependence on the substrate roughness, despite the orientation of the substrate textures. Interestingly, the crack spacing decreases with the increase of the roughness. Two possible mechanisms are proposed to understand the dependence of the cracks on roughness. Firstly, the concentration reduction of the drying suspension due to collecting colloidal particles from the substrate textures decreases the crack spacing. Secondly, stress concentration resulting from the defects (the notches in textures) in the dried deposition enhances crack formation. However, a quantitative estimation by the calculation of the stress concentrating factors reveals that the notch of the substrate textures dominates crack variation. The results here bring forth a practical method for controlling the crack orientation and suppression, and a potential application to crack-free coatings, films and paintings during the drying of complex fluids.

Direct observation of nanoparticle multiple-ring pattern formation during droplet evaporation with dark-field microscopy.

Controllable protocols towards nanoparticle self-assembly are important for applications of functional nanomaterials. Evaporation is a simple yet effective method to realize a gold nanoparticle ordered self-assembly, but until now, little attention has been paid to viewing the corresponding assembly process. Herein, with the help of dark-field microscopy, we in situ monitored the whole dynamic process of gold nanorod (GNR) assembly as the solvent evaporated. Differently from the previous coffee-ring effect, rod-shaped hydrophilic GNRs, within certain concentrations, spontaneously assembled into a multiple-ring pattern on a hydrophobic substrate via droplet drying. The self-assembly mechanism is consistent with a diffusion-driven kinetics, and the influencing factors, including the GNR surface modification, the colloid concentration, the surface property of the substrate, and the shape of the nanoparticles, were systematically investigated.

Controlling the Localization of Liquid Droplets in Polymer Matrices by Evaporative Lithography.

Localized inclusions of liquids provide solid materials with many functions, such as self-healing, secretion, and tunable mechanical properties, in a spatially controlled mode. However, a strategy to control the distribution of liquid droplets in solid matrices directly obtained from a homogeneous solution has not been reported thus far. Herein, we describe an approach to selectively localize liquid droplets in a supramolecular gel directly obtained from its solution by using evaporative lithography. In this process, the formation of droplet-embedded domains occurs in regions of free evaporation where the non-volatile liquid is concentrated and undergoes a phase separation to create liquid droplets prior to gelation, while a homogeneous gel matrix is formed in the regions of hindered evaporation. The different regions of a coating with droplet embedment patterns display different secretion abilities, enabling the control of the directional movement of water droplets.

Optical fiber with nanostructured cladding of TiO2 nanoparticles self-assembled onto a side polished fiber and its temperature sensing.

We demonstrated temperature sensing of a fiber with nanostructured cladding, which was constructed by titanium dioxide TiO2 nanoparticles self-assembled onto a side polished optical fiber (SPF). Significantly enhanced interaction between the propagating light and the TiO2 nanoparticles (TN) can be obtained via strong evanescent field of the SPF. The strong light-TN interaction results in temperature sensing with a maximum optical power variation of ~4dB in SPF experimentally for an external environment temperature varying from -7.8°C to 77.6°C. The novel temperature sensing device shows a linear correlation coefficient of better than 99.4%, and a sensitivity of ~0.044 dB/°C. The TN-based all-fiber-optic temperature sensing characteristics was successfully demonstrated, and it is compatible with fiber-optic interconnections and high potential in photonics applications.

Transition from Eu3+ to Eu2+ in SiO2 matrix prepared by sol-gel.

Activated silica matrix fluorescent materials doped with Al3+ and Eu2+ are prepared by sol-gel method. The effects of different atmospheres and annealing temperatures on luminescent properties are characterized by analysis techniques including X-ray diffraction, infrared spectroscopy and fluorescence spectra. When being excited at 281 nm wavelength, the fluorescent materials show a strong broad blue emission band, with the emission center at 430 nm and the FWHM of 56 nm. The results indicate that the blue emission is derived from 4f6 5d to 4f7 transition of the Eu2+ ions. Al3+ ion plays a key role in the process of deoxidization from Eu3+ to Eu2+. Al3+ and B3+ can enhance the blue-emission intensity. Also it is found that the highest luminescent intensity of the samples occurs in the sample Eu-03 annealed at 1150 degrees C in N2 atmosphere.

Anisotropic Diffusion of Elongated Particles in Active Coherent Flows.

The study of particle diffusion, a classical conundrum in scientific inquiry, holds manifold implications for various real-world applications. Particularly within the domain of active flows, where the motion of self-propelled particles instigates fluid movement, extensive research has been dedicated to unraveling the dynamics of passive spherical particles. This scrutiny has unearthed intriguing phenomena, such as superdiffusion at brief temporal scales and conventional diffusion at longer intervals. In contrast to the spherical counterparts, anisotropic particles, which manifest directional variations, are prevalent in nature. Although anisotropic behavior in passive fluids has been subject to exploration, enigmatic aspects persist in comprehending the interplay of anisotropic particles within active flows. This research delves into the intricacies of anisotropic passive particle diffusion, exposing a notable escalation in translational and rotational diffusion coefficients, as well as the superdiffusion index, contingent upon bacterial concentration. Through a detailed examination of particle coordinates, the directional preference of particle diffusion is not solely dependent on the particle length, but rather determined by the ratio of the particle length to the associated length scale of the background flow field. These revelations accentuate the paramount importance of unraveling the nuances of anisotropic particle diffusion within the context of active flows. Such insights not only contribute to the fundamental understanding of particle dynamics, but also have potential implications for a spectrum of applications.

From Chips-in-Lab to Point-of-Care Live Cell Device: Development of a Microfluidic Device for On-Site Cell Culture and High-Throughput Drug Screening.

Live cell assays provide real-time data of cellular responses. In combination with microfluidics, applications such as automated and high-throughput drug screening on live cells can be accomplished in small devices. However, their application in point-of-care testing (POCT) is limited by the requirement for bulky equipment to maintain optimal cell culture conditions. In this study, we propose a POCT device that allows on-site cell culture and high-throughput drug screening on live cells. We first observe that cell viabilities are substantially affected by liquid evaporation within the microfluidic device, which is intrinsic to the polydimethylsiloxane (PDMS) material due to its hydrophobic nature and nanopatterned surface. The unwanted PDMS-liquid-air interface in the cell culture environment can be eliminated by maintaining a persistent humidity of 95-100% or submerging the whole microfluidic device under water. Our results demonstrate that in the POCT device equipped with a water tank, both primary cells and cell lines can be maintained for up to 1 week without the need for external cell culture equipment. Moreover, this device is powered by a standard alkali battery and can automatically screen over 5000 combinatorial drug conditions for regulating neural stem cell differentiation. By monitoring dynamic variations in fluorescent markers, we determine the optimal doses of platelet-derived growth factor and epidermal growth factor to suppress proinflammatory S100A9-induced neuronal toxicities. Overall, this study presents an opportunity to transform lab-on-a-chip technology from a laboratory-based approach to actual point-of-care devices capable of performing complex experimental procedures on-site and offers significant advancements in the fields of personalized medicine and rapid clinical diagnostics.

Dynamics of endothelial cells migration in nature-mimicking blood vessels.

Endothelial cells (ECs) migration is a crucial early step in vascular repair and tissue neovascularization. While extensive research has elucidated the biochemical drivers of endothelial motility, the impact of biophysical cues, including vessel geometry and topography, remains unclear. Herein, we present a novel approach to reconstruct 3D self-assembly blood vessels-on-a-chip that accurately replicates real vessel geometry and topography, surpassing conventional 2D flat tube formation models. This vessels-on-a-chip system enables real-time monitoring of vasculogenesis and ECs migration at high spatiotemporal resolution. Our findings reveal that ECs exhibit increased migration speed and directionality in response to narrower vessel geometries, transitioning from a rounded to a polarized morphology. These observations underscore the critical influence of vessel size in regulating ECs migration and morphology. Overall, our study highlights the importance of biophysical factors in shaping ECs behavior, emphasizing the need to consider such factors in future studies of endothelial function and vessel biology.

Glycerol Droplet Spreading on Growing Bacillus Subtilis Biofilms.

Bacterial biofilm is a three-dimensional matrix composed of a large number of living bacterial individuals. The strong bio-interaction between the bacteria and its self-secreted matrix environment strengthens the mechanical integrity of the biofilm and the sustainable resistance of bacteria to antibiotics. As a soft surface, the biofilm is expected to present different dynamical wetting behavior in response to shear stress, which is, however, less known. Here, the spreading of liquid droplet on Bacillus subtilis biofilm at its different growing phases was experimentally investigated. Due to the viscoelastic response of the biofilm to fast spreading of the droplet, three stages were identified as inertial, viscous stages, and a longer transition in between. The physical heterogeneity of growing biofilm correlates with the spreading scaling within the inertial stage, followed by the possible chemical variation after a critical growing time. By using the duration of inertial spreading, the characteristic time scale was successfully linked to the shear modulus of the elastic dissipation of the biofilm. This measurement suggests a facile, non-destructive and in vivo method to understand the mechanical instability of this living matter.

Direct Observation of Nanotracer Transport in Swarming Bacteria during Antibiotic Adaptation.

Microorganisms inevitably encounter environmental variations and thus need to develop necessary strategies to adjust the colonies for survival. Here, we use cooperating Serratia marcescens bacteria to reveal how the whole population responds to a gradually deteriorating habitat. When subjected to antibiotics with increasing doses, the swarming bacteria transform weak homogeneous turbulent flows to nematic jet flows with defects and vortices on a large scale, by which bacteria exploit these coherent flows to transfer material and/or information. We elucidate a complete view of detailed spatiotemporal transport behavior in such microscale active turbulence with single-nanoparticle tracking. The nanoparticles in these active flows are brought into the state with the up limit of superdiffusion by the bacterial collective response to the stronger antibiotic stimulation. Strikingly, we found that, under the strengthening stimulation from antibiotics, bacteria with only a small fraction of their community get elongated and facilitate the drastic turbulence transition and an enhanced superdiffusion. These findings imply a possible collective response mechanism against environmental variations.

A Stand-Alone Microfluidic Chip for Long-Term Cell Culture.

Live-cell microscopy is crucial for biomedical studies and clinical tests. The technique is, however, limited to few laboratories due to its high cost and bulky size of the necessary culture equipment. In this study, we propose a portable microfluidic-cell-culture system, which is merely 15 cm×11 cm×9 cm in dimension, powered by a conventional alkali battery and costs less than USD 20. For long-term cell culture, a fresh culture medium exposed to 5% CO2 is programmed to be delivered to the culture chamber at defined time intervals. The 37 °C culture temperature is maintained by timely electrifying the ITO glass slide underneath the culture chamber. Our results demonstrate that 3T3 fibroblasts, HepG2 cells, MB-231 cells and tumor spheroids can be well-maintained for more than 48 h on top of the microscope stage and show physical characters (e.g., morphology and mobility) and growth rate on par with the commercial stage-top incubator and the widely adopted CO2 incubator. The proposed portable cell culture device is, therefore, suitable for simple live-cell studies in the lab and cell experiments in the field when samples cannot be shipped.