Alireza Mashaghi (@alirezamashaghi.bsky.social)

Research update from our lab: Dengue-on-a-chip and single-cell rheology reveal that Dengue is a "disease of mechanics"! #Bioengineering #Virology #Infection #Mechanobiology pubs.acs.org/doi/10.1021/...

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Revealing Mechanopathology Induced by Dengue NS1 Using Organ Chips and Single-Cell Force Spectroscopy Capillary leakage is a hallmark of severe dengue, yet its precise mechanisms remain elusive. Emerging evidence highlights the dengue virus’s targeting of mechanically active endothelial cells as a key contributor to dengue shock syndrome. The viral nonstructural protein 1 (NS1) has been identified as a central player, disrupting endothelial integrity and inducing vascular hyperpermeability independently of pro-inflammatory cytokines. This study provides a direct assessment of NS1-induced endothelial pathology by combining single-cell force spectroscopy and a microvessel-on-a-chip platform. We demonstrate that NS1 significantly alters endothelial cell mechanics, reducing cell stiffness and compromising junctional integrity, thereby directly linking these mechanical alterations to vascular dysfunction. These findings establish a framework for understanding the mechano-pathology of dengue and offer a platform for developing targeted therapeutic strategies to mitigate severe disease outcomes. https://pubs.acs.org/doi/10.1021/acsbiomaterials.4c02410#