Biophysical Society Thematic Meeting | Ascona 2026

Mechanobiology of Infection

Poster Abstracts

14-POS Board 14 LOCAL FORCES IN BACTERIAL ENVIRONMENTAL ADAPTATION Sergei I. Sukharev ; Elissa Moller; Andriy Anishkin University of Maryland, Biology, College Park, MD, USA

Freshwater is the primary transmission route for enteric pathogens and commensals, requiring robust adaptation to external osmolarity drops. To endure this drastic environmental shift, bacteria rapidly eject small metabolites via tension-activated inner-membrane channels, MscS and MscL, which are present in high numbers (~10^3 per cell). Because MscS is a highly conductive, low-tension-activated channel, a single opening risks instantly de-energizing the cell. How does this align with Δμ H+-based bacterial energetics? We propose that the activity of the MscS population is tightly regulated. During steady growth, most channels stay in a tension insensitive inactivated state but can be reactivated during osmotic shock to release osmolytes. (1) We have shown that the commonly observed splayed conformation of MscS is the inactivated state, stabilized by intercalating lipids separating the peripheral and central helices that form the gate. (2) Computational modeling predicts that the tension-receiving helices can be reconnected to the gate by applying turgor pressure (normal to the membrane), which pushes the gate toward the periplasm, expels lipids, and compacts the structure. (3) Independent analysis of light scattering traces from rapid-dilution experiments on bacterial suspensions indicated that, due to excess inner-membrane area, cells swell significantly (about twofold) before tension reaches the activation threshold for the channels. Given the peptidoglycan expansion modulus, turgor at this point rises to 8-12 atm, which could be sufficient to re-sensitize the inactivated MscS population. (4) After extensive solute release, the total cell volume decreases, increasing cytoplasmic macromolecular crowding that immediately inactivates MscS and terminates the permeability response. Therefore, the adaptive cycle of MscS tracks the sequential changes in local mechanical stress: a surge in turgor recharges the channels and prepares them to respond to tension. As a result, the entire MscS population can remain safely in a tension-insensitive state until osmotic shock occurs.

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