Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Poster Abstracts

15-POS Board 15 STRESS-INDUCED ASYMMETRIC REMODELING OF THE MYCOBACTERIAL ENVELOPE Lydia Mathew 1,2 ; Tzong-Hsien Lee 2 ; Marie-Isabel Aguilar 2 ; Shobhna Kapoor 1 ; 1 Indian Institute of Technology Bombay, Department of Chemistry, Mumbai, India 2 Monash University, Department of Biochemistry and Molecular Biology, Melbourne, Australia The mechanisms by which bacteria mechanically adapt to hostile host environments remain a key question in infection biology. Mycobacterium smegmatis (Msm), a surrogate for the mycobacterial community, encounters diverse stresses within the granuloma, including hypoxia and nutrient limitation. This study aims to elucidate how distinct environmental stresses modulate membrane mechanics and organization in Msm. To address this, we integrated Fluorescence Lifetime Imaging Microscopy (FLIM), Time-correlated Single-photon Counting (TCSPC), Atomic Force Microscopy (AFM), Fluorescence-activated Cell Sorting (FACS), and lipidomics to characterize membrane properties across scales, from molecular composition to mechanical behavior. Hypoxia induced asymmetric membrane reorganization, marked by the coexistence of domains with heterogeneous order and fluidity, as evidenced by lifetime heterogeneity. This suggests functional compartmentalization that balances structural integrity with adaptive pliability. In contrast, carbon starvation elicited a uniform mechanical response, characterized by global membrane rigidification, indicative of a protective adaptation to prolonged nutrient deprivation. Lipidomic profiling linked these stress-specific mechanical states to alterations in lipid saturation, geometry, and acyl chain length, establishing a direct relationship between lipid composition and membrane behavior. Notably, these findings demonstrate that bacterial membranes adopt condition-dependent mechanoadaptive strategies rather than uniform responses. Collectively, this work identifies membrane asymmetry and global rigidification as complementary principles underlying bacterial resilience. This multi scale framework connects lipidome remodeling to membrane mechanics and highlights membrane organization as a critical determinant of stress adaptation in host–pathogen contexts.

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