Membrane fusion is a vital process of life involved, for example, in cellular secretion via exocytosis, signaling between nerve cells, and virus infection. In both the life sciences and bioengineering, controlled membrane fusion has many possible applications, such as drug delivery, gene transfer, chemical microreactors, or synthesis of nanomaterials. Until now, the fusion dynamics has been elusive because direct observations have been limited to time scales that exceed several milliseconds. Here, the fusion of giant lipid vesicles is induced in a controlled manner and monitored with a temporal resolution of 50 micros. Two different fusion protocols are used that are based on synthetic fusogenic molecules and electroporation. For both protocols, the opening of the fusion necks is very fast, with an average expansion velocity of centimeters per second. This velocity indicates that the initial formation of a single fusion neck can be completed in a few hundred nanoseconds.
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http://dx.doi.org/10.1073/pnas.0602766103 | DOI Listing |
J Extracell Vesicles
January 2025
IPMC, UMR7275 CNRS-UniCA, INSERM U1323, team certified "Laboratory of Excellence (LABEX) Distalz", Valbonne, France.
Emerging evidence indicates that autophagy is tightly connected to the endocytic pathway. Here, we questioned the role of presenilins (PSENs 1 and 2), previously shown to be involved in autophagy regulation, in the secretion of small endocytic-originating extracellular vesicles known as exosomes. Indeed, while wild-type cells responded to stimuli promoting both multivesicular endosome (MVE) formation and secretion of small extracellular vesicles (sEVs) enriched in canonical exosomal proteins, PSEN-deficient cells were almost unaffected to these stimuli.
View Article and Find Full Text PDFFEBS Open Bio
January 2025
Institute of Neurophysiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany.
Neurotransmitter release is triggered in microseconds by the two C domains of the Ca sensor synaptotagmin-1 and by SNARE complexes, which form four-helix bundles that bridge the vesicle and plasma membranes. The synaptotagmin-1 CB domain binds to the SNARE complex via a 'primary interface', but the mechanism that couples Ca-sensing to membrane fusion is unknown. Widespread models postulate that the synaptotagmin-1 Ca-binding loops accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but these models do not seem compatible with SNARE binding through the primary interface, which orients the Ca-binding loops away from the fusion site.
View Article and Find Full Text PDFTransl Vis Sci Technol
January 2025
New England Eye Center, Tufts Medical Center, Boston, MA, USA.
Purpose: To evaluate visibility of a sub-band posterior to the external limiting membrane (ELM) and assess its age-associated variation.
Methods: In a retrospective cross-sectional study, normal eyes were imaged using a high-resolution spectral-domain optical coherence tomography (SD-OCT) prototype (2.7-µm axial resolution).
J Pharm Anal
December 2024
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 117004, China.
Gynecological cancers present significant treatment challenges due to drug resistance and adverse side effects. This review explores advancements in lysosomal escape mechanisms, essential for enhancing nano-therapeutic efficacy. Strategies such as pH-sensitive linkers and membrane fusion are examined, showcasing their potential to improve therapeutic outcomes in ovarian, cervical, and uterine cancers.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Departament de Nutrició, Ciències de l'Alimentació i Gastronomia, Facultat de Farmàcia i Ciències de l'Alimentació - Campus Torribera, Universitat de Barcelona, Prat de la Riba 171, 08921 Santa Coloma de Gramenet, Spain.
Assessing the binding mode of drug-like compounds is key in structure-based drug design. However, this may be challenged by factors such as the structural flexibility of the target protein. In this case, state-of-the-art computational methods can be valuable to explore the linkages between structural and pharmacological data.
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