Rahnamoun Ali, Kim Kyoungtea, Pedersen Joel A, Hernandez Rigoberto
Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218, United States.
Molecular and Environmental Toxicology Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States.
Langmuir. 2020 Mar 31;36(12):3149-3158. doi: 10.1021/acs.langmuir.9b03162. Epub 2020 Mar 12.
The interaction of lipopolysaccharides (LPS) with metal cations strongly affects the stability and function of the Gram-negative bacterial outer membrane. The sensitivity of deep rough (Re) LPS packing and function to the ionic environment, as affected by cation valency and ionic radius, has been determined using molecular dynamics simulations and Langmuir balance experiments. The degree of LPS aggregation within the LPS models in the presence of different cations is assessed by measuring the effective mean molecular area () of each LPS molecule projected onto the interfacial plane at the end of the equilibration. These results are compared to the LPS mean molecular area from experimental measurements in which the LPS monolayers are assembled at the air-water interface using a Langmuir film balance. We found that packing of the LPS arrays is sensitive to the ionic radius and ion valency of the cations present in solution during LPS array packing. Using enhanced sampling of the free energy for the intercalation of oligo(allylamine HCl) (OAH) into deep rough LPS bilayers, we obtained the affinity of the core section of LPS to OAH as a function of the nature of the metal cations present in solution. We found that packing of the solvated LPS bilayer models is sensitive to ionic radius and ion valency of the neutralizing cations. This further suggests that ion bridging and steric barriers rather than charge shielding are important factors in mitigating ligand intercalation under conditions with low ionic concentrations.
脂多糖（LPS）与金属阳离子的相互作用强烈影响革兰氏阴性菌外膜的稳定性和功能。利用分子动力学模拟和朗缪尔天平实验，已确定了深度粗糙（Re）LPS堆积和功能对离子环境的敏感性，该敏感性受阳离子价态和离子半径的影响。通过测量平衡结束时每个LPS分子投影到界面平面上的有效平均分子面积（），评估在不同阳离子存在下LPS模型中LPS的聚集程度。将这些结果与实验测量得到的LPS平均分子面积进行比较，在实验中，使用朗缪尔膜天平在空气-水界面组装LPS单层膜。我们发现，在LPS阵列堆积过程中，LPS阵列的堆积对溶液中存在的阳离子的离子半径和离子价态敏感。通过对低聚（烯丙胺盐酸盐）（OAH）插入深度粗糙LPS双层膜的自由能进行增强采样，我们得到了LPS核心部分对OAH的亲和力与溶液中存在的金属阳离子性质的函数关系。我们发现，溶剂化LPS双层膜模型的堆积对中和阳离子的离子半径和离子价态敏感。这进一步表明，在低离子浓度条件下，离子桥接和空间位垒而非电荷屏蔽是减轻配体插入的重要因素。
