New paradigms for bacteria sensing the world: molecular mechanisms of mechanosensation

Bacteria can thrive in fluctuating and extreme environments. Thus, a central question in biology concerns the mechanisms by which bacteria can adapt to stresses and the strategies they use for that purpose. Regulation of the internal and external osmotic forces across the cell membrane is one of the most fundamental processes bacteria employ to survive changes in the media osmolarity. At the center of this homeostatic strategy is the gating of mechanosensitive (MS) channels embedded in the plasma membrane of bacteria. We study cell survival in environments fluctuating in osmolyte concentrations using Bacillus Subtilis as a model system. For channel-less mutants, we systematically modulate the media exchange rate and quantify its effects on cell lysis. We find that high exchange rates lead to membrane topological defects that increase bacteria death probability when tension is applied to the membrane. Furthermore, for mutants with different combinations of MS channels, we find that the activation mechanism is channel-dependent: for channels of large conductance (MscL), the activation is loading rate-dependent, whereas, for channels of small conductance (MscS), the activation mechanism is membrane tension dependent. Moreover, we develop a model for cell lysis that captures the complexity of lipid dynamics and integrate that into the experimentally observed strategies of MS gating. Our results set a basis for a new paradigm of MS activation that, to our knowledge, has not yet been described.