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Frontiers in Bioengineering and... 2022Lipid vesicles are valuable mesoscale molecular confinement vessels for studying membrane mechanics and lipid-protein interactions, and they have found utility among...
Lipid vesicles are valuable mesoscale molecular confinement vessels for studying membrane mechanics and lipid-protein interactions, and they have found utility among bio-inspired technologies, including drug delivery vehicles. While vesicle morphology can be modified by changing the lipid composition and introducing fusion or pore-forming proteins and detergents, the influence of extramembrane crowding on vesicle morphology has remained under-explored owing to a lack of experimental tools capable of capturing morphological changes on the nanoscale. Here, we use biocompatible polymers to simulate molecular crowding , and through combinations of FRET spectroscopy, lifetime analysis, dynamic light scattering, and single-vesicle imaging, we characterize how crowding regulates vesicle morphology. We show that both freely diffusing and surface-tethered vesicles fluorescently tagged with the DiI and DiD FRET pair undergo compaction in response to modest concentrations of sorbitol, polyethylene glycol, and Ficoll. A striking observation is that sorbitol results in irreversible compaction, whereas the influence of high molecular weight PEG-based crowders was found to be reversible. Regulation of molecular crowding allows for precise control of the vesicle architecture , with vast implications for drug delivery and vesicle trafficking systems. Furthermore, our observations of vesicle compaction may also serve to act as a mechanosensitive readout of extramembrane crowding.
PubMed: 36394015
DOI: 10.3389/fbioe.2022.958026 -
Journal of Neuroscience Research Nov 2017Astrocytes are excitable neural cells that contribute to brain information processing via bidirectional communication with neurons. This involves the release of... (Review)
Review
Astrocytes are excitable neural cells that contribute to brain information processing via bidirectional communication with neurons. This involves the release of gliosignaling molecules that affect synapses patterning and activity. Mechanisms mediating the release of these molecules likely consist of non-vesicular and vesicular-based mechanisms. It is the vesicle-based regulated exocytosis that is an evolutionary more complex process. It is well established that the release of gliosignaling molecules has profound effects on information processing in different brain regions (e.g., hippocampal astrocytes contribute to long-term potentiation [LTP]), which has traditionally been considered as one of the cellular mechanisms underlying learning and memory. However, the paradigm of vesicle-based regulated release of gliosignaling molecules from astrocytes is still far from being unanimously accepted. One of the most important questions is to what extent can the conclusions obtained from cultured astrocytes be translated to in vivo conditions. Here, we overview the properties of vesicle mobility and their fusion with the plasma membrane in cultured astrocytes and compare these parameters to those recorded in astrocytes from acute brain hippocampal slices. The results from both experimental models are similar, which validates experiments on isolated astrocytes and further supports arguments in favor of in vivo vesicle-based exocytotic release of gliosignaling molecules. © 2017 Wiley Periodicals, Inc.
Topics: Animals; Astrocytes; Cell Membrane; Cells, Cultured; Exocytosis; Hippocampus; Long-Term Potentiation; Organ Culture Techniques; Rodentia; Synaptic Vesicles; Transport Vesicles
PubMed: 28370180
DOI: 10.1002/jnr.24051 -
Seminars in Cell & Developmental Biology Jul 2017Extracellular vesicles are nano-sized spherical bilayered proteolipids encasing various components. Cells of all domains of life actively release these vesicles to the... (Review)
Review
Extracellular vesicles are nano-sized spherical bilayered proteolipids encasing various components. Cells of all domains of life actively release these vesicles to the surroundings including various biological fluids. These extracellular vesicles are known to play pivotal roles in numerous pathophysiological functions. Extracellular vesicles have distinct characteristics, like high biocompatibility, safety, and nano-sized diameters that allow efficient drug loading capacity and long blood circulation half-life. These characteristics of extracellular vesicles have engrossed many scientists to harness them as new tools for novel delivery systems. This review will highlight the current state of the arts and problems of such extracellular vesicle-based theranostics, drug delivery and vaccines, and introduce "extracellular vesicle mimetics" as the novel alternative of extracellular vesicles. We hope to provide insights into the potential of extracellular vesicle mimetics as superior substitute to the natural extracellular vesicles that can be applied to theranostics, drug delivery, and vaccines against various diseases.
Topics: Animals; Biomimetic Materials; Drug Compounding; Drug Delivery Systems; Escherichia coli; Extracellular Vesicles; Humans; Meningitis, Bacterial; Nanostructures; Neisseria meningitidis; RNA, Small Interfering; Sepsis; Theranostic Nanomedicine; Vaccination; Vaccines
PubMed: 27916566
DOI: 10.1016/j.semcdb.2016.12.001 -
Journal of Controlled Release :... Jan 2024Extracellular vesicles are nanoscale vesicles that can be secreted by all cell types, are intracellular in origin and have the same composition as their parent cells,... (Review)
Review
Extracellular vesicles are nanoscale vesicles that can be secreted by all cell types, are intracellular in origin and have the same composition as their parent cells, play a key role in intercellular communication in organismal health and disease, and are now often used as biomarkers of disease and therapeutic agents in biomedical research. When injected locally or systemically, they have the ability to provide a variety of therapeutic effects, for example, regeneration of skin damage or restoration of cardiac function. However, direct injection of extracellular vesicles may result in their rapid clearance from the injection site.In order to maintain the biological activity of extracellular vesicles and to control the release of effective concentrations for better therapeutic efficacy during long-term disease treatment, the design of an optimized drug delivery system is necessary and different systems for the continuous delivery of extracellular vesicles have been developed. This paper first provides an overview of the biogenesis, composition and physiological function of extracellular vesicles, followed by a review of different strategies for extracellular vesicle isolation and methods for engineering extracellular vesicles. In addition, this paper reviews the latest extracellular vesicle delivery platforms such as micro-nanoparticles, injectable hydrogels, microneedles and scaffold patches. At the same time, the research progress and key cases of extracellular vesicle delivery systems in the field of biomedical therapeutics are described. Finally, the challenges and future trends of extracellular vesicle delivery are discussed.
Topics: Extracellular Vesicles; Drug Delivery Systems; Biomarkers; Biological Transport
PubMed: 38065416
DOI: 10.1016/j.jconrel.2023.11.057 -
FEBS Letters Nov 2018Vesicles in neurons and neuroendocrine cells store neurotransmitters and peptide hormones, which are released by vesicle fusion in response to Ca -evoking stimuli.... (Review)
Review
Vesicles in neurons and neuroendocrine cells store neurotransmitters and peptide hormones, which are released by vesicle fusion in response to Ca -evoking stimuli. Synaptotagmin-1 (Syt1), a Ca sensor, mediates ultrafast exocytosis in neurons and neuroendocrine cells. After vesicle docking, Syt1 has two main groups of binding partners: anionic phospholipids and the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) complex. The molecular mechanisms by which Syt1 triggers vesicle fusion remain controversial. This Review introduces and summarizes six molecular models of Syt1: (a) Syt1 triggers SNARE unclamping by displacing complexin, (b) Syt1 clamps SNARE zippering, (c) Syt1 causes membrane curvature, (d) membrane bridging by Syt1, (e) Syt1 is a vesicle-plasma membrane distance regulator, and (f) Syt1 undergoes circular oligomerization. We discuss important conditions to test Syt1 activity in vitro and attempt to illustrate the possible roles of Syt1.
Topics: Animals; Calcium; Exocytosis; Humans; Membrane Fusion; Models, Neurological; Protein Binding; SNARE Proteins; Synaptic Vesicles; Synaptotagmin I
PubMed: 30004579
DOI: 10.1002/1873-3468.13193 -
Frontiers in Cell and Developmental... 2020Pollen germination and pollen tube growth are important biological events in the sexual reproduction of higher plants, during which a large number of vesicle trafficking... (Review)
Review
Pollen germination and pollen tube growth are important biological events in the sexual reproduction of higher plants, during which a large number of vesicle trafficking and membrane fusion events occur. When secretory vesicles are transported via the F-actin network in proximity to the apex of the pollen tube, the secretory vesicles are tethered and fused to the plasma membrane by tethering factors and SNARE proteins, respectively. The coupling and uncoupling between the vesicle membrane and plasma membrane are also regulated by dynamic cytoskeleton, proteins, and signaling molecules, including small G proteins, calcium, and PIP2. In this review, we focus on the current knowledge regarding secretory vesicle delivery, tethering, and fusion during pollen germination and tube growth and summarize the progress in research on how regulators and signaling molecules participate in the above processes.
PubMed: 33553150
DOI: 10.3389/fcell.2020.615447 -
Synapse (New York, N.Y.) May 2015The ability of synapses to sustain neurotransmitter release during continuous activity critically relies on an efficient vesicle recycling program. Despite extensive... (Review)
Review
The ability of synapses to sustain neurotransmitter release during continuous activity critically relies on an efficient vesicle recycling program. Despite extensive research on synaptic function, the basic mechanisms of vesicle recycling remain poorly understood due to the relative inaccessibility of central synapses to conventional recording techniques. The extremely small size of synaptic vesicles, nearly five times below the diffraction-limited resolution of conventional light microscopy, has hampered efforts to define the mechanisms controlling their cycling. The complex sequence of dynamic processes that occur within the nerve terminals and link vesicle endocytosis and the subsequent round of release has been particularly difficult to study. The recent development of nanoscale-resolution imaging techniques has provided an opportunity to overcome these limitations and begin to reveal the mechanisms controlling vesicle recycling within individual nerve terminals. Here we summarize the recent advances in the implementation of super-resolution imaging and single-particle tracking approaches to study the dynamic steps of the vesicle recycling process within presynaptic terminals.
Topics: Animals; Exocytosis; Humans; Limit of Detection; Microscopy; Synaptic Vesicles
PubMed: 25522061
DOI: 10.1002/syn.21795 -
Applied and Environmental Microbiology Jun 2023Extracellular vesicles are small (approximately 50 to 250 nm in diameter), membrane-bound structures that are released by cells into their surrounding environment....
Extracellular vesicles are small (approximately 50 to 250 nm in diameter), membrane-bound structures that are released by cells into their surrounding environment. Heterogeneous populations of vesicles are abundant in the global oceans, and they likely play a number of ecological roles in these microbially dominated ecosystems. Here, we examine how vesicle production and size vary among different strains of cultivated marine microbes as well as explore the degree to which this is influenced by key environmental variables. We show that both vesicle production rates and vesicle sizes significantly differ among cultures of marine Proteobacteria, Cyanobacteria, and Bacteroidetes. Further, these properties vary within individual strains as a function of differences in environmental conditions, such as nutrients, temperature, and light irradiance. Thus, both community composition and the local abiotic environment are expected to modulate the production and standing stock of vesicles in the oceans. Examining samples from the oligotrophic North Pacific Gyre, we show depth-dependent changes in the abundance of vesicle-like particles in the upper water column in a manner that is broadly consistent with culture observations: the highest vesicle abundances are found near the surface, where the light irradiances and the temperatures are the greatest, and they then decrease with depth. This work represents the beginnings of a quantitative framework for describing extracellular vesicle dynamics in the oceans, which is essential as we begin to incorporate vesicles into our ecological and biogeochemical understanding of marine ecosystems. Bacteria release extracellular vesicles that contain a wide variety of cellular compounds, including lipids, proteins, nucleic acids, and small molecules, into their surrounding environment. These structures are found in diverse microbial habitats, including the oceans, where their distributions vary throughout the water column and likely affect their functional impacts within microbial ecosystems. Using a quantitative analysis of marine microbial cultures, we show that bacterial vesicle production in the oceans is shaped by a combination of biotic and abiotic factors. Different marine taxa release vesicles at rates that vary across an order of magnitude, and vesicle production changes dynamically as a function of environmental conditions. These findings represent a step forward in our understanding of bacterial extracellular vesicle production dynamics and provide a basis for the quantitative exploration of the factors that shape vesicle dynamics in natural ecosystems.
Topics: Seawater; Ecosystem; Cyanobacteria; Extracellular Vesicles; Water
PubMed: 37199672
DOI: 10.1128/aem.00594-23 -
Neuron May 2022Presynaptic active zones are molecular machines that control neurotransmitter secretion. They form sites for vesicle docking and priming and couple vesicles to Ca entry...
Presynaptic active zones are molecular machines that control neurotransmitter secretion. They form sites for vesicle docking and priming and couple vesicles to Ca entry for release triggering. The complexity of active zone machinery has made it challenging to determine its mechanisms in release. Simultaneous knockout of the active zone proteins RIM and ELKS disrupts active zone assembly, abolishes vesicle docking, and impairs release. We here rebuild docking, priming, and Ca secretion coupling in these mutants without reinstating active zone networks. Re-expression of RIM zinc fingers recruited Munc13 to undocked vesicles and rendered the vesicles release competent. Action potential triggering of release was reconstituted by docking these primed vesicles to Ca channels through attaching RIM zinc fingers to Caβ4-subunits. Our work identifies an 80-kDa β4-Zn protein that bypasses the need for megadalton-sized secretory machines, establishes that fusion competence and docking are mechanistically separable, and defines RIM zinc finger-Munc13 complexes as hubs for active zone function.
Topics: Action Potentials; Presynaptic Terminals; Synapses; Synaptic Transmission; Synaptic Vesicles
PubMed: 35176221
DOI: 10.1016/j.neuron.2022.01.026