Royal Jelly Derived Extracellular Vesicles Modulate Microglial Nanomechanics and Inflammatory Responses

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dc.catalogadorjca
dc.contributor.authorZavala, Gabriela
dc.contributor.authorBerríos, Pablo
dc.contributor.authorSandoval, Felipe
dc.contributor.authorBravo, Graciela
dc.contributor.authorBarrera, Nelson P.
dc.contributor.authorAlarcón Moyano, Jéssica
dc.contributor.authorDíaz Calderón, Paulo
dc.contributor.authorAguayo, Sebastián
dc.contributor.authorSchuh, Christina
dc.date.accessioned2025-04-28T16:52:37Z
dc.date.available2025-04-28T16:52:37Z
dc.date.issued2025
dc.description.abstractBACKGROUND Microglia, the braińs resident immune cells, undergo profound mechanical and functional changes upon activation contributing to neuroinflammation, a pathological signature of many neurological diseases. Thus, new anti-inflammatory treatment options are needed that tackle these mechanobiological alterations in microglia, which remain strongly understudied. In this context, extracellular vesicles (EVs) are crucial mediators of intercellular and interkingdom communication, yet their influence on the mechanobiological properties of recipient cells remains largely unknown. Honeybee-derived Royal Jelly EVs (RJEVs) have demonstrated remarkable anti-inflammatory properties, but their impact on microglial cellular nanomechanics and uptake mechanisms remains unclear. RESULTS In this study, we used a multi-disciplinary approach to analyze the resulting biological and nanomechanical changes following the activation of human microglia and the potential effect of RJEV treatment on these mechanobiological parameters. We observed that LPS treatment was associated with decreased cellular Young’s modulus, increased membrane fluidity, and enhanced motility of microglia, indicating a more migratory and pro-inflammatory phenotype. Additionally, LPS exposure altered cellular EV uptake mechanisms by shifting preference from an equilibrium of four mechanisms to the predominance of macropinocytosis and clathrin-dependent endocytosis. Remarkably, RJEV treatment counteracted these mechanobiological changes by, in turn, increasing microglial stiffness, reducing motility, and decreasing secretion of pro-inflammatory cytokines. CONCLUSION This is the first study to demonstrate that microglial activation state dictates EV uptake mechanisms and to establish a direct link between inflammation, cellular and membrane mechanics, and EV-mediated modulation. Our findings highlight RJEVs as promising candidates for regulating neuroinflammation by targeting microglial mechanobiology as well as opening new strategies for EV-based therapeutics
dc.fechaingreso.objetodigital2025-04-28
dc.format.extent32 páginas
dc.fuente.origenORCID
dc.identifier.doi10.1101/2025.03.03.641064
dc.identifier.urihttps://doi.org/10.1101/2025.03.03.641064
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/103485
dc.information.autorucInstituto de Ingeniería Biológica y Médica; Aguayo Paul, Sebastian Daniel; 0000-0003-0900-1993; 1062336
dc.language.isoen
dc.nota.accesocontenido completo
dc.rightsacceso abierto
dc.subject.ddc610
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleRoyal Jelly Derived Extracellular Vesicles Modulate Microglial Nanomechanics and Inflammatory Responses
dc.typepreprint
sipa.codpersvinculados1062336
sipa.trazabilidadORCID;2025-04-21
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