Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Poster Abstracts

19-POS Board 19 THE ROLE OF ENVIRONMENTAL MECHANICS ON COLONY MORPHOLOGY AND MYCOBACTERIAL CORD FORMATION Anna Rafalik 1 ; Richa Mishra 1 ; Heike Abendroth 1 ; Vivek V Thacker 1,2 ; 1 Heidelberg University Medical Faculty, Department of Infectious Diseases, Heidelberg, Germany 2 Heidelberg University Medical Faculty, Translational Lung Research Centre, Heidelberg, Germany Mycobacteria encompass major human pathogens, including M. tuberculosis (Mtb, the leading cause of death from a single infectious agent 1 ) and M. abscessus (Mabs, causing nontuberculous infections in patients with chronic lung conditions 2 ). Interestingly, many pathogenic mycobacteria form high-aspect-ratio, mechanically rigid cords, which suppress immune responses, harbor antibiotic-tolerant bacteria, and facilitate dissemination between neighboring cells 3 . The mechanisms driving cord formation and the role of biomechanics in mycobacterial infections remain poorly understood. Here, we adapted previously reported mechanically tunable yield-stress microgels 4 to observe how mycobacteria rearrange to form cords and understand the long-term effects of environmental stiffness on growth and colony morphology using three dimensional confocal imaging. We tuned hydrogel stiffness to mimic the yield stress of healthy (liquid-like, 0.2 Pa) and cystic fibrosis (stiff, 40 Pa) lung mucus, relevant to non-tuberculous mycobacterial diseases. Live-cell confocal imaging in high-yield-stress hydrogels (where Brownian motion is suppressed) revealed that the characteristic snapping mode of division and cord formation are tightly linked. In Mabs, the cording (Rough, R) morphotype aligns with the long axis of the cord after cell division, whereas the non-cording morphotype (Smooth, S) separates after division, forming disordered, low-aspect-ratio colonies. The shape of MabsS microcolonies is acutely sensitive to the hydrogel properties, with bacterial dispersion through the hydrogel sharply inhibited under high-yield-stress conditions. In contrast, the growth of MabsR or Mtb cords is relatively unconstrained by differences in environmental yield stress. Our findings suggest that environmental mechanics, e.g. viscoelastic properties of mucus, play an important role in shaping host-pathogen interactions and outcomes in mycobacterial infection and provide a biophysical framework for their analysis.1. Global Tuberculosis Report 2024, World Health Organization, 2024, ISBN: 978-92-4-010153-12. Dedrick et al., Clinical microbiology and infection, 2023, https://doi.org/10.1016/j.cmi.2023.06.0263. Mishra & Hannebelle et al., Cell, 2023, https://doi.org/10.1016/j.cell.2023.09.016 4. Hancock & Datta, Cell, 2024, https://doi.org/10.1016/j.bpj.2024.03.008

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