Publications

2024
Nan, L. ; Zhang, H. ; Weitz, D. A. ; Shum, H. C. Development and future of droplet microfluidics. Lab on a Chip 2024. Publisher's VersionAbstract
Over the past two decades, advances in droplet-based microfluidics have facilitated new approaches to process and analyze samples with unprecedented levels of precision and throughput. A wide variety of applications has been inspired across multiple disciplines ranging from materials science to biology. Understanding the dynamics of droplets enables optimization of microfluidic operations and design of new techniques tailored to emerging demands. In this review, we discuss the underlying physics behind high-throughput generation and manipulation of droplets. We also summarize the applications in droplet-derived materials and droplet-based lab-on-a-chip biotechnology. In addition, we offer perspectives on future directions to realize wider use of droplet microfluidics in industrial production and biomedical analyses.
nan2024.pdf
2023
Erkamp, N. A. ; Sneideris, T. ; Ausserwöger, H. ; Qian, D. ; Qamar, S. ; Nixon-Abell, J. ; St George-Hyslop, P. ; Schmit, J. D. ; Weitz, D. A. ; Knowles, T. P. J. Spatially non-uniform condensates emerge from dynamically arrested phase separation. Nature Communications 2023, 14, 684. Publisher's VersionAbstract
The formation of biomolecular condensates through phase separation from proteins and nucleic acids is emerging as a spatial organisational principle used broadly by living cells. Many such biomolecular condensates are not, however, homogeneous fluids, but possess an internal structure consisting of distinct sub-compartments with different compositions. Notably, condensates can contain compartments that are depleted in the biopolymers that make up the condensate. Here, we show that such double-emulsion condensates emerge via dynamically arrested phase transitions. The combination of a change in composition coupled with a slow response to this change can lead to the nucleation of biopolymer-poor droplets within the polymer-rich condensate phase. Our findings demonstrate that condensates with a complex internal architecture can arise from kinetic, rather than purely thermodynamic driving forces, and provide more generally an avenue to understand and control the internal structure of condensates in vitro and in vivo.
erkamp2023.pdf
Soltis, A. ; Zhelyazkova, B. ; Drake, P. ; Eleftheriadis, E. ; Ventresco, A. ; Weitz, D. A. ; Iafrate, A. J. ; Lee, A. High Throughput Microfluidics Platform to Assess Synthetic Lethality and Novel Therapeutic Drug Combinations. Blood 2023, 142, 7139. Publisher's Version soltis2023.pdf
Wu, Q. ; Huang, X. ; Liu, R. ; Yang, X. ; Xiao, G. ; Jiang, N. ; Weitz, D. A. ; Song, Y. Multichannel Multijunction Droplet Microfluidic Device to Synthesize Hydrogel Microcapsules with Different Core-Shell Structures and Adjustable Core Positions. Langmuir 2023. Publisher's VersionAbstract
Core–shell hydrogel microcapsules have sparked great interest due to their unique characteristics and prospective applications in the medical, pharmaceutical, and cosmetic fields. However, complex synthetic procedures and expensive costs have limited their practical application. Herein, we designed and prepared several multichannel and multijunctional droplet microfluidic devices based on soft lithography for the effective synthesis of core–shell hydrogel microcapsules for different purposes. Additionally, two different cross-linking processes (ultraviolet (UV) exposure and interfacial polymerization) were used to synthesize different types of core–shell structured hydrogel microcapsules. Hydrogel microcapsules with gelatin methacryloyl (GelMA) as the core and polyacrylamide (PAM) as the thin shell were synthesized using UV cross-linking. Using an interfacial polymerization process, another core–shell structured microcapsule with GelMA as the core and Ca2+ cross-linked alginate with polyethylenimine (PEI) as the shell was constructed, and the core diameter and total droplet diameter were flexibly controlled by carving. Noteworthy, these hydrogel microcapsules exhibit stimuli-responsiveness and controlled release ability. Overall, a novel technique was developed to successfully synthesize various hydrogel microcapsules with core–shell microstructures. The hydrogel microcapsules possess a multilayered structure that facilitates the coassembly of cells and drugs, as well as the layered assembly of multiple drugs, to develop synergistic therapeutic regimens. These adaptable and controllable hydrogel microdroplets shall held great promise for multicell or multidrug administration as well as for high-throughput drug screening.
wu2023.pdf
Xiao, Y. ; Huang, Q. ; Collins, J. W. ; Brouchon, J. ; Nelson, J. A. ; Niziolek, Z. ; O'Neil, A. ; Ye, F. ; Weitz, D. A. ; Heyman, J. A. The Rapid Generation of Cell-Laden, FACS-CompatibleCollagen Gels. Organoids 2023, 2 204-217. Publisher's VersionAbstract
A three-dimensional cell culture in hydrogel beads can support cell growth and differentiation into multi-cellular structures, and these gel beads could be used as building blocks for more complex three-dimensional assemblies. This requires hydrogel beads that are robust enough to sort via FACS yet can be degraded by cell-secreted enzymes. Collagen polymers form hydrogels that are excellent cell growth substrates; however, collagen-containing hydrogel beads typically include additional polymers that limit their degradation. Here, we introduce a simple microfluidic method to generate robust, sortable, cell-laden collagen hydrogel beads. We use on-device pH control to trigger collagen gelation without exposing cells to low pH, ensuring high cell viability. We fabricate microfluidic devices to generate droplets with a wide size range, as demonstrated by production of both small (~55 µm diameter) and large (~300 µm diameter) collagen gels. All hydrogels are sufficiently robust to allow for sorting using FACS. Moreover, high cell viability is maintained throughout the process.
xiao2023.pdf
Sun, S. ; Xue, N. ; Aime, S. ; Kim, H. ; Tang, J. ; McKinley, G. H. ; Stone, A. ; Weitz, D. A. Anomalous crystalline ordering of particles in a viscoelastic fluid under high shear. PNAS 2023, 120, e2304272120. Publisher's VersionAbstract
Addition of particles to a viscoelastic suspension dramatically alters the properties of the mixture, particularly when it is sheared or otherwise processed. Shear-induced stretching of the polymers results in elastic stress that causes a substantial increase in measured viscosity with increasing shear, and an attractive interaction between particles, leading to their chaining. At even higher shear rates, the flow becomes unstable, even in the absence of particles. This instability makes it very difficult to determine the properties of a particle suspension. Here, we use a fully immersed parallel plate geometry to measure the high-shear-rate behavior of a suspension of particles in a viscoelastic fluid. We find an unexpected separation of the particles within the suspension resulting in the formation of a layer of particles in the center of the cell. Remarkably, monodisperse particles form a crystalline layer which dramatically alters the shear instability. By combining measurements of the velocity field and torque fluctuations, we show that this solid layer disrupts the flow instability and introduces a single-frequency component to the torque fluctuations that reflects a dominant velocity pattern in the flow. These results highlight the interplay between particles and a suspending viscoelastic fluid at very high shear rates.
Sun2023.pdf
Shen, Y. ; Chen, A. ; Wang, W. ; Shen, Y. ; Ruggeri, F. S. ; Aime, S. ; Wang, Z. ; Qamar, S. ; Espinosa, J. R. ; Garaizar, A. ; et al. The liquid-to-solid transition of FUS is promoted by the condensate surface. PNAS 2023, 120, e2301366120. Publisher's VersionAbstract

A wide range of macromolecules can undergo phase separation, forming biomolecular condensates in living cells. These membraneless organelles are typically highly dynamic, formed reversibly, and carry out essential functions in biological systems. Crucially, however, a further liquid-to-solid transition of the condensates can lead to irreversible pathological aggregation and cellular dysfunction associated with the onset and development of neurodegenerative diseases. Despite the importance of this liquid-to-solid transition of proteins, the mechanism by which it is initiated in normally functional condensates is unknown. Here we show, by measuring the changes in structure, dynamics, and mechanics in time and space, that single-component FUS condensates do not uniformly convert to a solid gel, but rather that liquid and gel phases coexist simultaneously within the same condensate, resulting in highly inhomogeneous structures. Furthermore, our results show that this transition originates at the interface between the condensate and the dilute continuous phase, and once initiated, the gelation process propagates toward the center of the condensate. To probe such spatially inhomogeneous rheology during condensate aging, we use a combination of established micropipette aspiration experiments together with two optical techniques, spatial dynamic mapping and reflective confocal dynamic speckle microscopy. These results reveal the importance of the spatiotemporal dimension of the liquid-to-solid transition and highlight the interface of biomolecular condensates as a critical element in driving pathological protein aggregation.

shen2023.pdf
Xu, Z. ; Wang, Y. ; Sheng, K. ; Rosenthal, R. ; Liu, N. ; Hua, X. ; Zhang, T. ; Chen, J. ; Song, M. ; Lv, Y. ; et al. Droplet-based high-throughput single microbe RNA sequencing by smRandom-seq. Nature Communications 2023, 14, 5130. Publisher's VersionAbstract

Bacteria colonize almost all parts of the human body and can differ significantly. However, the population level transcriptomics measurements can only describe the average bacteria population behaviors, ignoring the heterogeneity among bacteria. Here, we report a droplet-based high-throughput single-microbe RNA-seq assay (smRandom-seq), using random primers for in situ cDNA generation, droplets for single-microbe barcoding, and CRISPR-based rRNA depletion for mRNA enrichment. smRandom-seq showed a high species specificity (99%), a minor doublet rate (1.6%), a reduced rRNA percentage (32%), and a sensitive gene detection (a median of ~1000 genes per single E. coli). Furthermore, smRandom-seq successfully captured transcriptome changes of thousands of individual E. coli and discovered a few antibiotic resistant subpopulations displaying distinct gene expression patterns of SOS response and metabolic pathways in E. coli population upon antibiotic stress. smRandom-seq provides a high-throughput single-microbe transcriptome profiling tool that will facilitate future discoveries in microbial resistance, persistence, microbe-host interaction, and microbiome research.

xu2023.pdf
Svetlizky, I. ; Kim, S. ; Weitz, D. A. ; Spaepen, F. Dislocation interactions during plastic relaxation of epitaxial colloidal crystals. Nature Communications 2023, 14, 5760. Publisher's VersionAbstract

The severe difficulty to resolve simultaneously both the macroscopic deformation process and the dislocation dynamics on the atomic scale limits our understanding of crystal plasticity. Here we use colloidal crystals, imaged on the single particle level by high-speed three-dimensional (3D) confocal microscopy, and resolve in real-time both the relaxation of the epitaxial misfit strain and the accompanying evolution of dislocations. We show how dislocation interactions give rise to the formation of complex dislocation networks in 3D and to unexpectedly sharp plastic relaxation. The sharp relaxation is facilitated by attractive interactions that promote the formation of new dislocations that are more efficient in mediating strain. Dislocation networks form fragmented structures, as dislocation growth is blocked by either attractive interactions, which result in the formation of sessile dislocation junctions, or by repulsion from perpendicular segments. The strength of these blocking mechanisms decreases with the thickness of the crystal film. These results reveal the critical role of dislocation interactions in plastic deformation of thin films and can be readily generalized from the colloidal to the atomic scale.

svetlizky2023.pdf
Morse, D. B. ; Michalowski, A. M. ; Ceribelli, M. ; De Jonghe, J. ; Vias, M. ; Riley, D. ; Davies-Hill, T. ; Voss, T. ; Pittaluga, S. ; Muus, C. ; et al. Positional influence on cellular transcriptional identity revealed through spatially segmented single-cell transcriptomics. Cell Systems 2023, 14, P464-481. Publisher's VersionAbstract
Single-cell RNA sequencing (scRNA-seq) is a powerful technique for describing cell states. Identifying the spatial arrangement of these states in tissues remains challenging, with the existing methods requiring niche methodologies and expertise. Here, we describe segmentation by exogenous perfusion (SEEP), a rapid and integrated method to link surface proximity and environment accessibility to transcriptional identity within three-dimensional (3D) disease models. The method utilizes the steady-state diffusion kinetics of a fluorescent dye to establish a gradient along the radial axis of disease models. Classification of sample layers based on dye accessibility enables dissociated and sorted cells to be characterized by transcriptomic and regional identities. Using SEEP, we analyze spheroid, organoid, and in vivo tumor models of high-grade serous ovarian cancer (HGSOC). The results validate long-standing beliefs about the relationship between cell state and position while revealing new concepts regarding how spatially unique microenvironments influence the identity of individual cells within tumors.
morse2023.pdf
Rosenthal, R. G. ; Zhang, X. D. ; Durdic, K. I. ; Collins, J. J. ; Weitz, D. A. Controlled Continuous Evolution of Enzymatic Activity Screened at Ultrahigh Throughput Using Drop-Based Microfluidics. Angewandte Chemie 2023, 62, e202303112. Publisher's VersionAbstract
Enzymes are highly specific catalysts delivering improved drugs and greener industrial processes. Naturally occurring enzymes must typically be optimized which is often accomplished through directed evolution; however, this is still a labor- and capital-intensive process, due in part to multiple molecular biology steps including DNA extraction, in vitro library generation, transformation, and limited screening throughput. We present an effective and broadly applicable continuous evolution platform that enables controlled exploration of fitness landscape to evolve enzymes at ultrahigh throughput based on direct measurement of enzymatic activity. This drop-based microfluidics platform cycles cells between growth and mutagenesis followed by screening with minimal human intervention, relying on the nCas9 chimera with mutagenesis polymerase to produce in vivo gene diversification using sgRNAs tiled along the gene. We evolve alditol oxidase to change its substrate specificity towards glycerol, turning a waste product into a valuable feedstock. We identify a variant with a 10.5-fold catalytic efficiency.
rosenthal2023.pdf
Zhang, Y. ; Zhao, X. ; Han, P. ; He, T. ; Yin, H. ; Zhang, L. ; Feng, Y. ; Weitz, D. A. Rock-on-a-chip: “Seeing” the association/disassociation of an adaptive polymer in solutions flowing through porous media. Lab on a Chib 2023, 23, 2808-2818. Publisher's VersionAbstract
The flow and transport of polymer solutions through porous media are ubiquitous in myriad scientific and engineering applications. With escalating interest in adaptive polymers, understanding the flow dynamics of their solutions is indispensable (yet lacking). Here, the hydrophobic-effect-driven reversible associations in a self-adaptive polymer (SAP) solution and its flow characteristics in a microfluidic-based “rock-on-a-chip” device have been analyzed. The hydrophobic aggregates were fluorescent labeled; this enabled a direct visualization of the in situ association/disassociation of the polymer supramolecular assemblies in pore spaces and throats. Furthermore, the influence of this adaptation on the macroscopic flow behavior of the SAP solution was analyzed by comparing its flow with that of two partially-hydrolyzed polyacrylamide (the molecular weight (MW)-equivalent HPAM-1 and ultrahigh-MW HPAM-2) solutions in the semi-dilute regime with similar initial viscosities. At low flow rates (with shear predominance), the SAP solution showed a low shear viscosity compared to HPAM-1, indicating a higher shear susceptibility for association than chain entanglement. Although the SAP exhibited the same elastic instability as the non-adaptive polymers above a threshold flow rate, the adaptable structure of the former advanced the onset of its viscoelastic-governed flow, providing a stronger flow resistance, possibly through an extension resistance. Furthermore, 3D-media analysis indicated that the reversible association/disassociation of SAP increased the accessible pore space during nonaqueous-liquid displacement, facilitating oil production.
zhang2023.pdf
Battat, S. ; Nagarkar, A. A. ; Spaepen, F. ; Weitz, D. A. ; Whitesides, G. M. Kinetics of formation of a macroscale binary Coulombic material. Physical Review Materials 2023, 7 L040401. Publisher's VersionAbstract
The electrostatic self-assembly of charged Brownian objects typically occurs in cases of short-range interactions. The objects form Coulombic materials that are close-packed and have long-range order. Here, we present a system in which two kinds of non-Brownian millimeter-sized beads tribocharge differently, experience long-range electrostatic interactions, and still form ordered two-dimensional structures. We provide a complete characterization of the kinetics of formation of these materials, as the total number of beads is held constant and the relative number of beads that tribocharge negatively or positively is modified. We agitate the beads by shaking the dish in which they are contained. We show that the beads commonly adopt a transient structure that we call a rosette. A rosette consists of a central bead surrounded by six close-packed neighbors of a different kind. The symmetry of the final structure depends on the relative number of negatively and positively charged beads, and it is not necessarily the same as that of the transient structure. Our results bear important implications in the de novo design of Coulombic materials given our ability to isolate transient structures, identify the moment of their appearance, and quantify the impact of agitation, tribocharging, and Coulombic energy minimization on their persistence.
battat2023.pdf
Zhang, Y. ; Zhao, X. - Z. ; Han, P. - H. ; Zhang, L. - Y. ; Weitz, D. A. ; Feng, Y. - J. Visualization of adaptive polymer flow and displacement in medium-permeable 3D core-on-a-chip. Petroleum Science 2023, 20, 1018-1029. Publisher's VersionAbstract
Polymer flooding has been witnessed an effective technology for enhancing oil recovery from medium-to low-permeability reservoirs; however, direct visualization of polymer solution flow in such reservoir condition is still lacking. In this work, a three-dimensional (3D) core-on-a-chip device with a permeability of around 200 mD was prepared and employed to visualize the pore-scale flow and displacement of a self-adaptive polymer (SAP, 8.7 × 106 g·mol−1)−whose microscopic association structure and macroscopic viscosity can reversibly change in response to shear action−versus partially hydrolyzed polyacrylamide(HPAM), by recording their flow curves, monitoring dynamic transportation process via particle imaging velocimetry, and building 3D structure of remaining oil. The results show that, in single-phase flow, all polymer solutions exhibit flow thinning and then thickening regions as flow rate increases, but the transition between two regimes occurs at a small Weissenberg number (10−3−10−1) in this medium-permeable condition. In contrast to HPAM-1 with close weight-average molecular weight (Mw), the adaptive character not only extends SAP's shear-govern region, allowing SAP to propagate piece by piece and achieve higher accessible pore volume, but it also enhances the elastic resistibility of polymer in the extension-dominated regime, increasing the microscopic displacement efficiency. These two effects result in 1.5–3 times more oil recovery factor for SAP than for HPAM-1. Regarding ultra-high-Mw HPAM-2 (25 × 106 g·mol−1), plugging and chain degradation do occur, thus producing lower oil recovery than SAP. This work provides a direct approach for in-situ assessment of polymer-based displacing system under a more authentic condition of practical reservoirs.
zhang2023.pdf
Battat, S. ; Weitz, D. A. ; Whitesides, G. M. Melting of a macroscale binary Coulombic crystal. Soft Matter 2023, 19, 3190-3198. Publisher's VersionAbstract
The question of melting has been addressed theoretically and experimentally for two-dimensional crystals in thermal equilibrium. However, as it pertains to out-of-equilibrium systems, the question is unresolved. Here, we present a platform to study the melting of a two-dimensional, binary Coulombic crystal composed of equal numbers of nylon and polytetrafluoroethylene (PTFE) beads that measure a couple of millimeters in diameter. The beads are tribocharged—nylon positively and PTFE negatively—and they experience long-range electrostatic interactions. They form a square crystal in which nylon and PTFE beads sit at alternating sites on a checkerboard lattice. We melt the crystal by agitating the dish in which it resides using an orbital shaker. We compare the melting behavior of the crystal without impurities to that of the crystal with impurities, where we use gold-coated nylon beads as impurities because they tribocharge negligibly. Our results reveal that impurities do not influence the melting of the crystal. Instead, the crystal undergoes shear-induced melting, beginning from its edges, due to its collisions with the dish. As a result of repetitive collisions, the beads acquire kinetic energy, undergo rearrangements, and become disordered. Unlike most examples of shear-induced melting, portions of the crystal remain locally ordered given the persistence of electrostatic interactions and the occurrence of some collisions that are favorable to ordering clusters of beads. Our work clarifies the melting behavior of sheared crystals whose constituents have persistent long-range interactions. It may prove valuable in determining the conditions under which such materials are immune to disorder.
battat2023.pdf
Elosegui-Artola, A. ; Gupta, A. ; Najibi, A. J. ; Seo, B. R. ; Garry, R. ; Tringides, C. M. ; de Lázaro, I. ; Darnell, M. ; Gu, W. ; Zhou, Q. ; et al. Matrix viscoelasticity controls spatiotemporal tissue organization. Nature Materials 2023, 22, 117–127. Publisher's VersionAbstract
Biomolecular and physical cues of the extracellular matrix environment regulate collective cell dynamics and tissue patterning. Nonetheless, how the viscoelastic properties of the matrix regulate collective cell spatial and temporal organization is not fully understood. Here we show that the passive viscoelastic properties of the matrix encapsulating a spheroidal tissue of breast epithelial cells guide tissue proliferation in space and in time. Matrix viscoelasticity prompts symmetry breaking of the spheroid, leading to the formation of invading finger-like protrusions, YAP nuclear translocation and epithelial-to-mesenchymal transition both in vitro and in vivo in a Arp2/3-complex-dependent manner. Computational modelling of these observations allows us to establish a phase diagram relating morphological stability with matrix viscoelasticity, tissue viscosity, cell motility and cell division rate, which is experimentally validated by biochemical assays and in vitro experiments with an intestinal organoid. Altogether, this work highlights the role of stress relaxation mechanisms in tissue growth dynamics, a fundamental process in morphogenesis and oncogenesis.
elosegui-artola2023.pdf
Yang, C. ; Xiao, Y. ; Hu, L. ; Chen, J. ; Zhao, C. - X. ; Zhao, P. ; Ruan, J. ; Wu, Z. ; Yu, H. ; Weitz, D. A. ; et al. Stimuli-Triggered Multishape, Multimode, and Multistep Deformations Designed by Microfluidic 3D Droplet Printing. small 2023, 22, 2207073. Publisher's VersionAbstract

Elastomers generally possess low Young's modulus and high failure strain, which are widely used in soft robots and intelligent actuators. However, elastomers generally lack diverse functionalities, such as stimulated shape morphing, and a general strategy to implement these functionalities into elastomers is still challenging. Here, a microfluidic 3D droplet printing platform is developed to design composite elastomers architected with arrays of functional droplets. Functional droplets with controlled size, composition, position, and pattern are designed and implemented in the composite elastomers, imparting functional performances to the systems. The composited elastomers are sensitive to stimuli, such as solvent, temperature, and light, and are able to demonstrate multishape (bow- and S-shaped), multimode (gradual and sudden), and multistep (one- and two-step) deformations. Based on the unique properties of droplet-embedded composite elastomers, a variety of stimuli-responsive systems are developed, including designable numbers, biomimetic flowers, and soft robots, and a series of functional performances are achieved, presenting a facile platform to impart diverse functionalities into composite elastomers by microfluidic 3D droplet printing.

yang2023.pdf
Yang, G. ; Liu, Y. ; Jin, S. ; Hui, Y. ; Wang, X. ; Xu, L. ; Chen, D. ; Weitz, D. A. ; Zhao, C. - X. Phase separation-induced nanoprecipitation for making polymer nanoparticles with high drug loading. Aggregate 2023, 4 e314. Publisher's VersionAbstract

Increasing drug loading remains a critical challenge in the development and translation of nanomedicine. High drug-loading nanoparticles have demonstrated unique advantages such as less carrier material used, better-controlled drug release, and improved efficacy and safety. Herein, we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading (up to 66.5 wt%) based on phase separation-induced nanoprecipitation. Upon addition of salt, phase separation occurs in a miscible solvent-water solution delaying the precipitation time of drugs and polymers to different extents, facilitating their co-precipitation thus the formation of high drug-loading nanoparticles with high encapsulation efficiency (>90%) and excellent stability (>1 month). This technology is versatile and easy to be adapted to various hydrophobic drugs, different polymers, and solvents. This salt-induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading, and opens great potentials for future nanomedicines.

yang2023.pdf
Niu, M. ; Cao, W. ; Wang, Y. ; Zhu, Q. ; Luo, J. ; Wang, B. ; Zheng, H. ; Weitz, D. A. ; Zong, C. Droplet-based transcriptome profiling of individual synapses. Nature Biotechnology 2023, 41, 1332–1344. Publisher's VersionAbstract

Synapses are crucial structures that mediate signal transmission between neurons in complex neural circuits and display considerable morphological and electrophysiological heterogeneity. So far we still lack a high-throughput method to profile the molecular heterogeneity among individual synapses. In the present study, we develop a droplet-based single-cell (sc) total-RNA-sequencing platform, called Multiple-Annealing-and-Tailing-based Quantitative scRNA-seq in Droplets, for transcriptome profiling of individual neurites, primarily composed of synaptosomes. In the synaptosome transcriptome, or ‘synaptome’, profiling of both mouse and human brain samples, we detect subclusters among synaptosomes that are associated with neuronal subtypes and characterize the landscape of transcript splicing that occurs within synapses. We extend synaptome profiling to synaptopathy in an Alzheimer’s disease (AD) mouse model and discover AD-associated synaptic gene expression changes that cannot be detected by single-nucleus transcriptome profiling. Overall, our results show that this platform provides a high-throughput, single-synaptosome transcriptome profiling tool that will facilitate future discoveries in neuroscience.

niu2023.pdf
Xiao, Y. ; Yang, C. ; Zhai, X. ; Zhao, L. ; Zhao, P. ; Ruan, J. ; Chen, D. ; Weitz, D. A. ; Liu, K. Bioinspired Tough and Strong Fibers with Hierarchical Core-Shell Structure. Advanced Materials Interfaces 2023, 10, 2201962. Publisher's VersionAbstract

Strong and tough bio-based fibers are attractive for both fundamental research and practical applications. In this work, strong and tough hierarchical core–shell fibers with cellulose nanofibrils (CNFs) in the core and regenerated silk fibroins (RSFs) in the shell are designed and prepared, mimicking natural spider silks. CNF/RSF core–shell fibers with precisely controlled morphology are continuously wet-spun using a co-axial microfluidic device. Highly-dense non-covalent interactions are introduced between negatively-charged CNFs in the core and positively-charged RSFs in the shell, diminishing the core/shell interface and forming an integral hierarchical fiber. Meanwhile, shearing by microfluidic channels and post-stretching induce a better ordering of CNFs in the core and RSFs in the shell, while ordered CNFs and RSFs are more densely packed, thus facilitating the formation of non-covalent interactions within the fiber matrix. Therefore, CNF/RSF core–shell fibers demonstrate excellent mechanical performances; especially after post-stretching, their tensile strength, tensile strain, Young's modulus, and toughness are up to 635 MPa, 22.4%, 24.0 GPa, and 110 MJ m−3, respectively. In addition, their mechanical properties are barely compromised even at −40 and 60 °C. Static load and dynamic impact tests suggest that CNF/RSF core–shell fibers are strong and tough, making them suitable for advanced structural materials.

xiao2023.pdf

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