Post-surgical adhesions are triggered by calcium-dependent membrane bridges between mesothelial surfaces

• DOI: 10.1038/s41467-020-16893-3
• Publication Date: 2020-06-17T10:05:00Z
• Authors: Adrian Fischer; Tim Koopmans; Pushkar Ramesh; Simon Christ; Maximilian Strunz; Juliane Wannemacher; Michaela Aichler; Annette Feuchtinger; Axel Walch; Meshal Ansari; Fabian J. Theis; Kenji Schorpp; Kamyar Hadian; Philipp-Alexander...; Herbert B. Schiller; Yuval Rinkevich
• Keywords: Male; 0301 basic medicine; Science; Article; Epithelium; Cell Line; Mice; 03 medical and health sciences; Cytosol; Imaging, Three-Dimensional; Postoperative Complications; Cell Adhesion; Animals; Humans; Calcium Signaling; RNA, Small Interfering; Cytoskeleton; Principal Component Analysis; Q; Cell Membrane; Computational Biology; Mice, Inbred C57BL; Disease Models, Animal; Calcium; Female

Abstract Surgical adhesions are bands of scar tissues that abnormally conjoin organ surfaces. Adhesions a major cause post-operative and dialysis-related complications, yet their patho-mechanism remains elusive, prevention agents in clinical trials have thus far failed to achieve efficacy. Here, we uncover the adhesion initiation mechanism by coating beads with human mesothelial cells normally line surfaces, viewing them under stimuli. We document expansive membrane protrusions from mesothelia tether massive accompanying adherence forces. Membrane precede matrix deposition, can transmit stimuli healthy identify cytoskeletal effectors calcium signaling as molecular triggers initiate surgical adhesions. A single, localized dose targeting these early germinal events completely prevented preclinical mouse model, assays. Our findings classifies pathology originating bridges offer radically new therapeutic approach treat