Liu Jie, Zhou Jian
School of Chemistry and Chemical Engineering, Guangdong Provincial Key Lab for Green Chemical Product Technology, South China University of Technology, Guangzhou 510640, PR China.
School of Chemistry and Chemical Engineering, Guangdong Provincial Key Lab for Green Chemical Product Technology, South China University of Technology, Guangzhou 510640, PR China.
Acta Biomater. 2016 Aug;40:23-30. doi: 10.1016/j.actbio.2016.04.044. Epub 2016 Apr 29.
Understanding the mechanism of the antimicrobial and antifouling properties of mixed charged materials is of great significance. The interactions between human gamma fibrinogen (γFg) and mixed carboxylic methyl ether-terminated (COOCH3-) and trimethylamino-terminated (N(CH3)3(+)-) SAMs and the influence of hydrolysis were studied by molecular simulations. After hydrolysis, the mixed SAMs exhibit behaviors from antimicrobial to antifouling, since the COOCH3-thiols were translated into carboxylic acid (COO(-)-) terminated thiols, which carried a net charge of -1 e. Simulation results showed that the main differences between COOCH3-/N(CH3)3(+)-SAM and COO(-)-/N(CH3)3(+)-SAM are the charged property and the hydration layer above the surface. γFg could stably adsorb on the positively-charged COOCH3-/N(CH3)3(+)-SAM. The adsorption behavior is mainly induced by the strong electrostatic attraction. There is a single hydration layer bound to the surface, which is related to the N(CH3)3(+) groups. The van der Waals repulsion between γFg and the single hydration layer are not strong enough to compensate the strong electrostatic attraction. After hydrolysis, the positively-charged SAM was transferred to a neutral mixed charged surface, the electrostatic attraction between γFg and the surface disappears. Meanwhile, the SAM surface is covered by double hydration layers, which is induced by the N(CH3)3(+) and COO(-) groups; water molecules around COO(-) groups are obviously denser than that around N(CH3)3(+) groups. With the combined contribution from double hydration layers and the vanishment of electrostatic attraction, γFg is forced to desorb from the surface. After hydrolysis, the internal structure of mixed SAM appears more ordered due to the electrostatic interactions between charged groups on the top of SAMs.
The antimicrobial and antifouling materials are of great importance in many biological applications. The strong hydration property of surfaces and the interactions between proteins and surfaces play a key role in resisting protein adsorption. The mixed SAMs, constructed from a 1:1 combination of COOCH3- and N(CH3)3(+)-terminated thiols, can induce protein adsorption mainly through the electrostatic interaction. When the COOCH3-terminated thiols were hydrolyzed to negatively charged COO(-)-terminated thiols, the mixed-charged SAMs switched from antimicrobial to antifouling. Due to the strong hydration property of the mixed charged SAMs, the adsorbed γFg moved away from the surface. Understanding the interactions between protein and mixed-charged SAMs in the atomistic level is important for the practical design and development of new antimicrobial and antifouling materials.
了解混合带电材料的抗菌和防污性能机制具有重要意义。通过分子模拟研究了人γ-纤维蛋白原（γFg）与混合的羧基甲基醚封端（COOCH3-）和三甲氨基封端（N(CH3)3(+)-）自组装单分子膜（SAMs）之间的相互作用以及水解的影响。水解后，混合SAMs表现出从抗菌到防污的行为，因为COOCH3-硫醇转化为羧酸（COO(-)-）封端的硫醇，其净电荷为-1e。模拟结果表明，COOCH3-/N(CH3)3(+)-SAM和COO(-)-/N(CH3)3(+)-SAM之间的主要差异在于表面的带电性质和水化层。γFg可以稳定地吸附在带正电的COOCH3-/N(CH3)3(+)-SAM上。吸附行为主要由强静电引力诱导。表面结合有单层水化层，这与N(CH3)3(+)基团有关。γFg与单层水化层之间的范德华排斥力不足以补偿强静电引力。水解后，带正电的SAM转变为中性混合带电表面，γFg与表面之间的静电引力消失。同时，SAM表面被双层水化层覆盖，这是由N(CH3)3(+)和COO(-)基团诱导的；COO(-)基团周围的水分子明显比N(CH3)3(+)基团周围的水分子密集。由于双层水化层的综合作用以及静电引力的消失，γFg被迫从表面解吸。水解后，由于SAM顶部带电基团之间的静电相互作用，混合SAM的内部结构显得更加有序。
抗菌和防污材料在许多生物应用中具有重要意义。表面的强水化性质以及蛋白质与表面之间的相互作用在抵抗蛋白质吸附方面起着关键作用。由COOCH3-和N(CH3)3(+)-封端的硫醇按1:1组合构建的混合SAMs主要通过静电相互作用诱导蛋白质吸附。当COOCH3-封端的硫醇水解为带负电的COO(-)-封端的硫醇时，混合带电SAMs从抗菌转变为防污。由于混合带电SAMs的强水化性质，吸附的γFg从表面移开。在原子水平上理解蛋白质与混合带电SAMs之间的相互作用对于新型抗菌和防污材料的实际设计和开发很重要。
