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In colloidal suspensions containing large and small particles, a peculiar attractive force caused by entropy appears, this force can cause aggregation of large particles. With the concentration of small particles increasing, the large particles can be endocytosed by vesicle. A continuum model is developed to investigate the equilibrium mechanics between a biomembrane and an enveloped colloidal particle with different aspect ratios. The results show that the endocytosis of colloidal particle depends on the aspect ratio of colloidal particle. For a spherical colloidal particle (aspect ratio is zero), the entropy provides sufficient favorable energy to drive its engulfment; however, at a high aspect ratio, the entropy is not sufficient to overcome the resistance from the biomembrane and causes endocytosis.

The quantitative characterization of endocytic vesicles in images acquired with microscope is critically important for deciphering of endocytosis mechanisms. Image segmentation is the most important step of quantitative image analysis. In spite of availability of many segmentation methods, the accurate segmentation is challenging when the images are heterogeneous with respect to object shapes and signal intensities what is typical for images of endocytic vesicles. We present a Morphological reconstruction and Contrast mapping segmentation method (MrComas) for the segmentation of the endocytic vesicle population that copes with the heterogeneity in their shape and intensity. The method uses morphological opening and closing by reconstruction in the vicinity of local minima and maxima respectively thus creating the strong contrast between their basins of attraction. As a consequence, the intensity is flattened within the objects and their edges are enhanced. The method accurately recovered quantitative characteristics of synthetic images that preserve characteristic features of the endocytic vesicle population. In benchmarks and quantitative comparisons with two other popular segmentation methods, namely manual thresholding and Squash plugin, MrComas shows the best segmentation results on real biological images of EGFR (Epidermal Growth Factor Receptor) endocytosis. As a proof of feasibility, the method was applied to quantify the dynamical behavior of Early Endosomal Autoantigen 1 (EEA1)-positive endosome subpopulations during EGF-stimulated endocytosis.

This study theoretically investigates receptor–ligand-mediated endocytosis of nanoparticles (NPs) in wall shear flow. The endocytosis is modeled as a birth–death process and relationships between coefficients in the model and the wall shear rate have been derived to deal with the effects of the shear flow. Model predictions show that flow-induced alteration in bond formation rates does not affect the endocytosis significantly, and the suppression of hydrodynamic load on endocytosis is eminent only when diameters of NPs are large (around 700nm) and the shear rate is sufficiently high. In the latter case, it is shown that the hydrodynamic load suppresses the initial attachment of NPs to cells more than the following internalization. The model also predicts that shear-promoted expression of certain ligands can lead to observable increase in the number of endocytozed NPs in typical flow-chamber experiments, and the promotion can also cause selective endocytosis of NPs by cells at high shear rate regions if the ligand surface density on NPs or the original expression of receptors on cells in the absence of flow is low.

We directly visualized the uptake and intracellular vesicle transport of shortened single walled carbon nanotubes in living cells through a dual-labeling system. With a stable labeling of fluorescein isothiocyanate and a pH-sensitive stacking of doxorubicin on carbon nanotubes, the location of internalized nanotubes inside the cell and the microenvironment especially the pH change of the nanotube-embedded vesicles could be monitored at the same time. Results showed that after internalization through endocytic pathway, carbon nanotubes tended to transport from the early endosomes to later acidic lysosomes and these vesicles moved along the microtubule track toward a perinuclear region where is a microtubule-organizing center. These results might provide a novel understanding for the intracellular interaction of carbon nanotubes and living cells.

Titanium dioxide nanoparticles (TiO₂ NPs) are widely used in photodynamic therapy (PDT) of cancer treatment as excellent regenerative photocatalysts. However, there are some challenges because of their poor dispersity. Transferrin (Tf) was tried to modify the surface of TiO₂ NPs to reduce the aggregation, which further affected uptake and excretion on SMMC-7721 human liver cancer cells. Initially, TiO₂ NPs modified with Tf (TiO₂-Tf NPs) entered into the cells faster than the pure TiO₂ NPs which remain attaching on the cell membrane after short-term co-incubation. Tf modification increased the rate and amount of cellular endocytosis. Both TiO₂ NPs and TiO₂-Tf NPs were observed in lysosomes after long-term co-incubation through clathrin-mediated endocytosis pathway. Expulsion of NPs was then observed and it was found that the exocytosis of TiO₂-Tf NPs was fast in the first 24 h, and then slowed down gradually from 24 h to 144 h. Totally, existence of Tf decreased the exocytosis of TiO₂ NPs. Furthermore, the differences of cytotoxicity and genotoxicity between TiO₂ NPs and TiO₂-Tf NPs show that surface-adsorbed Tf components provide some protection from the cytotoxic effect by reducing the production of intracellular ROS. TiO₂-Tf NPs obviously affected cell cycle, indicating a significant G2/M phase cell cycle arrest. Our results offer a promising application of easily aggregated TiO₂ NPs in the nanomedicine field.

In biological development, morphogens are locally produced and spread to other regions in organs, forming gradients that control the inter-related pattern and growth of developing organs. Mechanisms of morphogen transport were built and investigated by numerical simulations in [A. D. Lander, Q. Nie and F. Y. M. Wan, Do morphogen gradients arise by diffusion? Developmental Cell2 (2002) 785–796]. In that paper, model C, which considers endocytosis, exocytosis and receptor synthesis and degradation, is in a one-dimensional spatial region and couples a partial differential equation with ordinary differential equations. Here, this model is promoted to an arbitrary dimension bounded region. We prove existence, uniqueness and non-negativity of a global solution for this advanced model, of its steady-state solution and linear stability of steady state by operator semigroup, the Schauder theorem and local perturbation method. Our results improve previous results for this model in a one dimension region.

Clathrin- and caveolae-mediated endocytosis are the most commonly used pathways for the internalization of cell membrane receptors. However, due to their dimensions are within the diffraction limit, traditional fluorescence microscopy cannot distinguish them and little is known about their interactions underneath cell membrane. In this study, we proposed the line-switching scanning imaging mode for dual-color triplet-state relaxation (T-Rex) stimulated emission depletion (STED) super-resolution microscopy. With this line-switching mode, the cross-talk between the two channels, the side effects from pulse picker and image drift in frame scanning mode can be effectively eliminated. The dual-color super-resolution imaging results in mixed fluorescent beads validated the excellent performance. With this super-resolution microscope, not only the ring-shaped structure of clathrin and caveolae endocytic vesicles, but also their semi-fused structures underneath the cell membrane were distinguished clearly. The resultant information will greatly facilitate the study of clathrin- and caveolae-mediated receptor endocytosis and signaling process and also our home-built dual-color T-Rex STED microscope with this line-switching imaging mode provides a precise and convenient way to study subcellular-scale protein interactions.

The development of nanoscale delivery vehicles for siRNAs is a current topic of considerable importance. However, little is understood about the exact trafficking mechanisms for siRNA-vehicle complexes across the plasma membrane and into the cytoplasm. While some information can be gleaned from studies on delivery of plasmid DNA, the different delivery requirements for these two vehicles makes drawing specific conclusions a challenge. However, using chemical inhibitors of different endocytosis pathways, studies on which endocytotic pathways are advantageous and deleterious for the delivery of nucleic acid drugs are emerging. Using this information as a guide, it is expected that the future development of effective siRNA delivery vehicles and therapeutics will be greatly improved.

Understanding the endocytosis and intracellular trafficking of short interfering RNA (siRNA) delivery vehicle complexes remains a critical bottleneck in designing siRNA delivery vehicles for highly active RNA interference (RNAi)-based therapeutics. In this study, we show that dextran functionalization of silica nanoparticles enhanced uptake and intracellular delivery of siRNAs in cultured cells. Using pharmacological inhibitors for endocytotic pathways, we determined that our complexes are endocytosed via a previously unreported mechanism for siRNA delivery in which dextran initiates scavenger receptor-mediated endocytosis through a clathrin/caveolin-independent process. Our findings suggest that siRNA delivery efficiency could be enhanced by incorporating dextran into existing delivery platforms to activate scavenger receptor activity across a variety of target cell types.

Four properties define exosomes. First, they are tiny bodies–as small as 35 nm in diameter, 1,000 times less than the width of a human hair—that perform key assignments in cell signaling and other biological processes. Second, their size aids in transiting hard-to-navigate tissue boundaries in the body, such as the brain–blood barrier and the gut–blood barrier, optioning an oral administration of therapy in some instances. Third, since they can convey protein peptides, nucleic acids, and small molecule drugs, they represent an amalgam of proteomic, genomic, and lipidomic concepts in biomedicine. And fourth, it is conceivable, exosomes can address any human disease—many of which cannot be accessed today—even using material from other species. Two research groups—in St. Louis and Montreal—first characterized them almost simultaneously in 1984, offering an explanation of how immature red blood cells lost their iron-transporting transferrin receptor when they matured. Their role as intercellular communicators grew in 1996 when researchers at the University of Utrecht showed how exosomes induced a powerful immune response that caused cancerous tumors to regress. They travel in every body fluid: blood, lymph, urine, tears, saliva, cerebrospinal, and mother’s milk. Originally seen in electron micrographs and thought to be inconsequential, they now have a presence in biotechnology as a new platform for diagnostics and therapy, broadly representing proteome medicine. As yet, they have not reached a critical mass for clinical adoption, though their prospects are tantalizing. This piece ends with a prediction—that by 2034, the 50th anniversary of the term exosome, proteome medicine will have several generally recognized as safe and effective exosome-based prescriptions, with China leading the way.