Zwitterionic Osmolytes Revive Surface Charges under Salt Stress via Dual Mechanisms

To counter the stress of a salt imbalance, the cell often produces low molecular weight osmolytes to resuscitate homeostasis. However, how zwitterionic osmolytes would tune the electrostatic interactions among charged biomacromolecular surfaces under salt stress has eluded mainstream investigations. Here, via combination of molecular simulation and experiment, we demonstrate that a set of zwitterionic osmolytes is able to restore the electrostatic interaction between two negatively charged surfaces that had been masked in the presence of salt. Interestingly, the mechanisms of resurrecting charge interaction under excess salt are revealed to be mutually divergent and osmolyte specific. In particular, glycine is found to competitively desorb the salt ions from the surface via its direct interaction with the surface. On the contrary, TMAO and betaine counteract salt stress by retaining adsorbed cations but partially neutralizing their charge density via ion-mediated interaction. These access to alternative modes of osmolytic actions would provide the cell the required flexibility in combating salt stress.