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The outer membrane (OM) of Gram-negative bacteria is asymmetrical with its outer layer mainly populated with polyanionic lipopolysaccharide (LPS). Much empirical evidence shows how OM permeability can be altered electrostatically: if Mg(2+) or divalent cations are required for the integrity of the OM, antimicrobial peptides (AMPs) or ethylene-diaminetetraacetic acid (EDTA) can permeabilize it. Using a coarse-grained model of the outer LPS layer, in which the layer is viewed as forming discrete binding sites for opposite charges, we study how the LPS layer can be modified electrostatically. In particular, we capture systematically ion-pairing and lateral-charge correlations on the LPS layer. Our results offer a clear picture of (competitive) ion binding onto the LPS layer and its impact on the lateral packing of LPS molecules, similarly to what has been seen in experiments: divalent cations such as Mg(2+) not only neutralize the LPS layer but also make its planar charge distribution heterogeneous, thus tightening the LPS layer; on the other hand, polycationic AMPs or polyanionic EDTA can displace Mg(2+) ions from the LPS layer and counteract the favorable effect of Mg(2+). Our result will be useful for clarifying to what extent OM permeability can be modified electrostatically.

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