Synapses are semi-membraneless, protein-dense, sub-micron chemical reaction compartments responsible for signal processing in each and every neuron. Proper formation and dynamic responses to ...stimulations of synapses, both during development and in adult, are fundamental to functions of mammalian brains, although the molecular basis governing formation and modulation of compartmentalized synaptic assemblies is unclear. Here, we used a biochemical reconstitution approach to show that, both in solution and on supported membrane bilayers, multivalent interaction networks formed by major excitatory postsynaptic density (PSD) scaffold proteins led to formation of PSD-like assemblies via phase separation. The reconstituted PSD-like assemblies can cluster receptors, selectively concentrate enzymes, promote actin bundle formation, and expel inhibitory postsynaptic proteins. Additionally, the condensed phase PSD assemblies have features that are distinct from those in homogeneous solutions and fit for synaptic functions. Thus, we have built a molecular platform for understanding how neuronal synapses are formed and dynamically regulated.
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•Biochemical reconstitution reveals PSD assembly formation via phase separation•The ePSD condensates cluster NMDA receptor and promote actin bundle formation•The ePSD condensates selectively enrich SynGAP and actively exclude gephyrin•The ePSD condensates can be modulated by activity-dependent protein modifications
Phase transition-mediated formation of excitatory postsynaptic density condensates revealed by biochemical reconstitutions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The formation of new mineral phases in confined environments, especially in porous media, is crucial for various geological processes like mineralization and diagenesis. The nucleation and ...precipitation of minerals are initiated at the microscale through fluid‐rock interaction, where dissolution of primary phases leads to supersaturated conditions and nucleation and growth of secondary ones. Previous research has focused primarily on either precipitation or nucleation, without fully exploring their combined impact. Our study introduces a computational framework that integrates classical nucleation theory with the micro‐continuum method. We validated our model by comparing with experiments, and discovered that different surface nucleation rate changes the mode of precipitation from a preferential to uniform precipitate textures. Furthermore, our study uncovered that the conventional deterministic precipitation method tends to underestimate the permeability of the porous matrix. In contrast, the new framework significantly improves model accuracy by incorporating preferential precipitation and heterogeneous nucleation.
Plain Language Summary
The formation of minerals in confined environments, especially in porous media, is important for both natural processes and industrial applications. The resulting solid phases can greatly affect the porosity and permeability of the porous structure. Many previous studies have focused on either nucleation or precipitation, we still have a limited understanding of how both processes interact at different scales. In this study, we integrated the Darcy‐Brinkman‐Stokes method and classical nucleation theory to investigate the interplay between nucleation, precipitation, species transport, and their impact on permeability. Our findings show that adjusting the surface nucleation rates can change the mode of mineral precipitation from preferential to uniform. We also found that the traditional deterministic precipitation method underestimates permeability in certain scenario. Therefore, considering probabilistic nucleation is crucial when there is preferential precipitation and heterogeneous nucleation on the interfaces between the minerals and surrounding liquid under reactive flow conditions.
Key Points
The proposed computational framework focuses on investigating the heterogeneity of nucleation and its effects on mineral precipitation
The new model is validated by comparing with experimental data, demonstrating an agreement in both nucleation morphology and rate
The new model integrates probabilistic nucleation, resulting in a notable enhancement in the accuracy of permeability predictions
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Cell migration plays important roles in many biological processes, but how migrating cells orchestrate intracellular molecules and subcellular structures to regulate their speed and ...direction is still not clear. Here, by characterizing the intracellular diffusion and the three-dimensional lamellipodium structures of fish keratocyte cells, we observe a strong positive correlation between the intracellular diffusion and cell migration speed and, more importantly, discover a switching of cell migration modes with reversible intracellular diffusion variation and lamellipodium structure deformation. Distinct from the normal fast mode, cells migrating in the newly-found slow mode have a deformed lamellipodium with swollen-up front and thinned-down rear, reduced intracellular diffusion and compartmentalized macromolecule distribution in the lamellipodium. Furthermore, in turning cells, both lamellipodium structure and intracellular diffusion dynamics are also changed, with left-right symmetry breaking. We propose a mechanism involving the front-localized actin polymerization and increased molecular crowding in the lamellipodium to explain how cells spatiotemporally coordinate the intracellular diffusion dynamics and the lamellipodium structure in regulating their migrations.
Edible bird’s nest (EBN) has been consumed as a Chinese delicacy for hundreds of years; the functions of which have been proposed to prevent lung disease, strengthen immune response, and restore skin ...youthfulness. To support the skin function of EBN, the water extract and the enzymatic digest of EBN with enriched digested peptides were tested in cultured keratinocyte, HaCaT cell line. The effects of EBN extract and digest in inducing proteins crucial for skin moisturizing were determined in both
in vitro
and
ex vivo
models. In cultured keratinocytes, the expressions of S100-fused type proteins contributing to skin barrier function in the stratum corneum, e.g. filaggrin and filaggrin-2, were determined in both mRNA and protein levels, which were markedly induced in the treatment of EBN extract or digest. The EBN-induced gene transcriptions of filaggrin and filaggrin-2 were mediated by activation of p38 MAPK pathway and various transcription factors, e.g. GATA3, PPARα, PPARβ, and PPARγ: these transcriptional factors were markedly activated by the digested products of EBN, as compared to the extract, in cultured keratinocytes. By using atomic force microscopy (AFM), the EBN-treated keratinocyte was shown to have more liquid-like morphology, as compared to a control cell. The EBN digest showed better induction on these moisturizing effects as compared to the extract. These lines of evidence therefore suggested the water moisturizing effect of EBN in skin function.
In this work, we developed a simple method to fabricate a thickness-based continuous stiffness gradient for biological studies. It was made by glass slides, polydimethylsiloxane （PDMS） pre-polymer, ...spacer and clips only, without any sophisticated equipment. It is easy to fabricate in any general biological and pharmaceutical laboratories. The stiffness gradient was characterized in terms of apparent Young＇s modulus by atomic force microscopy （AFM） and the Young＇s modulus along the gradient was found to be 8.5- 120 kPa, which is within the physiological relevant range. HeLa-C3 ceils were cultured on the gradient to study their morphological behavior according to the substrate stiffness. Furthermore, the drug efficiency of etoposide, an anti-cancer drug, was studied along the substrate stiffness gradient. It was found that HeLa-C3 cells cultured on the soft region of the gradient （8.5-11 kPa） are more sensitive to etoposide. We believe the proposed device could promote cell investigations and drug screenings on a substrate with comparable stiffness to the native tissue.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The effect of extracellular matrix (ECM) stiffness on embryonic trophoblast cells invasion during mammalian embryo implantation remains largely unknown. In this study, we investigated the effects of ...ECM stiffness on various aspects of human trophoblast cell behaviors during cell-ECM interactions. The mechanical microenvironment of the uterus was simulated by fabricating polyacrylamide (PA) hydrogels with different levels of stiffness. The human choriocarcinoma (JAR) cell lineage was used as the trophoblast model. We found that the spreading area of JAR cells, the formation of focal adhesions, and the polymerization of the F-actin cytoskeleton were all facilitated with increased ECM stiffness. Significantly, JAR cells also exhibited durotactic behavior on ECM with a gradient stiffness. Meanwhile, stiffness of the ECM affects the invasion of multicellular JAR spheroids. These results demonstrated that human trophoblast cells are mechanically sensitive, while the mechanical properties of the uterine microenvironment could play an important role in the implantation process.
Artificial micro/nanomotors using active particles hold vast potential in applications such as drug delivery and microfabrication. However, upgrading them to micro/nanorobots capable of performing ...precise tasks with sophisticated functions remains challenging. Bubble microthruster (BMT) is introduced, a variation of the bubble‐driven microrobot, which focuses the energy from a collapsing microbubble to create an inertial impact on nearby target microparticles. Utilizing ultra‐high‐speed imaging, the microparticle mass and density is determined with sub‐nanogram resolution based on the relaxation time characterizing the microparticle's transient response. Master curves of the BMT method are shown to be dependent on the viscosity of the solution. The BMT, controlled by a gamepad with magnetic‐field guidance, precisely manipulates target microparticles, including bioparticles. Validation involves measuring the polystyrene microparticle mass and hollow glass microsphere density, and assessing the mouse embryo mass densities. The BMT technique presents a promising chip‐free, real‐time, highly maneuverable strategy that integrates bubble microrobot‐based manipulation with precise bioparticle mass and density detection, which can facilitate microscale bioparticle characterizations such as embryo growth monitoring.
This work demonstrates a substantial progress of using swimming microrobots to perform precise tasks with sophisticated functions. This magnetic‐field‐guided bubble microthruster technique presents a promising chip‐free, real‐time, highly maneuverable strategy that integrates bubble microrobot‐based manipulation with precise bioparticle mass and density detection with sub‐nanogram resolution. This technique can facilitate microscale bioparticle characterizations such as embryo growth monitoring.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
How to accurately characterize the modulus of living cells at the whole-cell level with a well-defined measurement geometry and precise mathematical modeling of viscoelastic relaxation is an ongoing ...challenge in biophysics and mechanobiology. Here, we report combined atomic-force-microscopy (AFM) measurements of stress relaxation and indentation force for 10 cell types ranging from epithelial, muscle, and neuronal cells to blood and stem cells, from which we obtain a unified quantitative description of the compressive modulus E(t) of individual living cells. The cell modulus E(t) is found to have an initial exponential decay at short times t followed by a long-time power-law decay together with a persistent modulus. The three components of E(t) at different timescales thus provide a digital spectrum of mechanical readouts that are closely linked to the hierarchical structure and active stress of living cells. This work provides a reliable experimental framework that can be utilized to characterize the mechanical state of living cells and investigate their physiological functions and diseased states.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM, UPUK
We report direct atomic-force-microscope measurements of capillary force hysteresis (CFH) of a circular contact line (CL) formed on a long glass fiber, which is coated with a thin layer of soft ...polymer film and intersects a water-air interface. The measured CFH shows a distinct overshoot for the depinning of a static CL, and the overshoot amplitude grows logarithmically with both the hold time τ and fiber speed V. A unified model based on the slow growth of a wetting ridge and force-assisted barrier crossing is developed to explain the observed time (or state) and speed (or rate) dependent CL depinning dynamics over an aging soft surface. The experimental findings have important implications to a common class of problems involving depinning dynamics in a defect or roughness landscape, such as friction of solid interfaces.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
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