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bioRxiv · 10.64898/2026.10.23.761342

When do bacterial mechanosensitive channels get activated?

S B, S. S.·Albarran, O.·Garces, R.·Eldredge, J. D.·Sukharev, S.·Schmidt, C. F.
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Abstract

Bacterial cell envelopes are complex multilayer structures that combine mechanical protection with a multitude of transport and sensory functions. Bacteria maintain substantial turgor pressures which is needed to withstand external forces, grow and maintain shape. An osmotic downshock can create fatal pressure levels. To survive, bacteria rapidly release osmolytes, mainly ions and small metabolites, through mechanosensitive channels (Mscs). Mscs are embedded in the plasma membrane (PM) and act as pressure/tension-activated valves, reducing pressure and preserving cell integrity. It is not well understood, however, how overall stresses are distributed among the layers of the cell envelope, and, in particular, when tension would be borne by the PM and felt by the channels. In this study, we numerically and analytically examine stress distributions within a two-layer model of the cell envelope under varying turgor pressure. We use experimentally determined parameters for PM and peptidoglycan (PG) elasticities, and include enzyme/antibiotic induced weakening of the PG. We introduce, as a critical parameter, a PM reservoir, without which an observed substantial area increase during the shock would not be possible without PM rupture. We used finite-element simulations to model cell swelling assuming linear elasticity of the envelope components, and analytical calculations to model nonlinear PG strain hardening. We analyzed tension sharing between PG and PM with varying PM reservoir sizes during osmotic downshocks. We estimate that an envelope area increase of slightly more than 50% would occur at a turgor pressure of ~11 atm and would be sufficient to fully unfold a 50% PM reservoir and also generate sufficient PM tension to activate mechanosensitive channels. A softening of the PG layer with lysozyme or {beta}-lactam antibiotics is predicted to increase cell expansion at a given turgor pressure and trigger earlier activation of mechanosensitive channels, leading to increased, deleterious metabolite loss.

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S B, S. S., Albarran, O., Garces, R., Eldredge, J. D., Sukharev, S., Schmidt, C. F.. 2026-10-24. When do bacterial mechanosensitive channels get activated?. https://doi.org/10.64898/2026.10.23.761342

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