Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Monday Speaker Abstracts

PROBING THE CONTRIBUTION OF ACTIN NETWORK ARCHITECTURE AND CORTICAL MECHANICS IN BACTERIAL-INDUCED HOST CELL FUSION Megan K Chong ; Matthew D Welch University of California, Berkeley, Molecular & Cell Biology, Berkeley, CA, USA Bacteria from the pseudomallei group of Burkholderia species, a group of Gram-negative, facultative intracellular bacteria, spread by inducing host cell-cell fusion to form multinucleate giant cells. Host cell fusion relies on the polymerization of actin at the bacterial surface, generating an actin network, and driving actin-based motility. When moving bacteria collide with the plasma membrane, bacteria extend into plasma-membrane protrusions that push into neighboring cells. Fusion occurs within these protrusions, but it remains unclear what molecular and mechanical mechanisms mediate this cell-cell fusion and spread. Specifically, how distinct actin network architectures impact protrusion extension dynamics and host cell fusion efficiency, and whether host cell mechanics (e.g. membrane and cortical tension) promote or constrain cell cell fusion, are not known. Here, we use live-cell imaging to compare dynamics between bacteria expressing actin-based motility effectors from different Burkholderia species. We find that bacterial force generation depends on actin network architecture, with branched Arp2/3-mediated actin networks extending protrusions significantly faster and farther and undergoing fewer reversals than bundled actin networks generated via an Ena/VASP-like mechanism. Additionally, reducing host cell cortical contractility by myosin II inhibition leads to more processive movement of bacteria within protrusions and longer protrusions for bacteria that polymerize bundled but not branched actin networks. This suggests an active interplay between the actin mediated forces generating protrusions and the resistive forces at the host cell boundary that may determine the rate of bacterial induced cell-cell fusion. Ongoing experiments will measure how protrusion dynamics impact cell-cell fusion, and how membrane tension changes in response to protrusions. This work will provide a framework for how Burkholderia species hijack underlying host cell biology to mediate infections and how mammalian cell mechanics and molecular co factors both promote and constrain cell-cell fusion and bacterial spread.

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