Lipophilicity of Cationic Ligands Promotes Irreversible Adsorption of Nanoparticles to Lipid Bilayers.
Lipophilicity of Cationic Ligands Promotes Irreversible Adsorption of Nanoparticles to Lipid Bilayers.
复制标题
阳离子配体的亲脂性促进纳米颗粒对脂质双层的不可逆吸附。
DOI：
10.1021/acsnano.0c09732
复制
发表时间：
2021-04-27
期刊：
影响因子：
17.1
通讯作者：
Pedersen, Joel A.
中科院分区：
文献类型：
--
作者：
Lochbaum, Christian A.;Chew, Alex K.;Zhang, Xianzhi;Rotello, Vincent;Van Lehn, Reid C.;Pedersen, Joel A.
关键词：
工程纳米材料的表面性质如何影响其与细胞的相互作用的机械理解是必不可少的设计材料的应用，如生物成像和药物输送，以及评估纳米材料的安全性。配体包覆的金纳米颗粒已被广泛研究，因为它们高度可调的表面性质使得能够研究配体官能化对与生物系统相互作用的影响。亲脂性配体已通过膜破坏与不良生物学结果相关，但配体亲脂性与膜相互作用之间的关系尚不清楚。在这里，我们使用的2纳米金纳米粒子上涂覆的阳离子配体库探测配体端基亲脂性的相互作用与支持的磷脂酰胆碱脂质双层作为细胞质膜的模型的影响。用石英晶体微天平研究了纳米粒子在模型膜上的吸附和脱附。我们发现，纳米粒子吸附模型膜增加配体亲脂性。原子分子动力学模拟进一步分析了配体结构对金纳米颗粒附着的影响，结果表明，增加配体亲脂性促进配体嵌入脂质双层。总之，实验和模拟结果可以用一个两态模型来描述，该模型考虑了初始附着和随后向准不可逆结合态的转化。我们发现，在我们的纳米粒子库中，只有最亲脂性配体包被的纳米粒子进行转换的准不可逆状态。我们建议，最初的连接是由配体和磷脂尾基之间的相互作用，而转化成准不可逆的结合状态反映了磷脂尾基之间的配体嵌入和最终从双层脂质提取。配体亲脂性的系统变化使我们能够证明，阳离子配体的亲脂性与纳米粒子双层吸附，并表明，改变非极性配体R基团促进配体嵌入到与不可逆吸附相关的双层的机制。
A mechanistic understanding of how the surface properties of engineered nanomaterials influence their interactions with cells is essential for designing materials for applications such as bioimaging and drug delivery, as well as for assessing nanomaterial safety. Ligand-coated gold nanoparticles have been widely investigated because their highly tunable surface properties enable investigations into the effect of ligand functionalization on interactions with biological systems. Lipophilic ligands have been linked to adverse biological outcomes through membrane disruption, but the relationship between ligand lipophilicity and membrane interactions is not well understood. Here, we use a library of cationic ligands coated on 2-nm gold nanoparticles to probe the impact of ligand end group lipophilicity on interactions with supported phosphatidylcholine lipid bilayers as a model for cytoplasmic membranes. Nanoparticle adsorption to and desorption from the model membranes were investigated by quartz crystal microbalance with dissipation monitoring. We find that nanoparticle adsorption to model membranes increases with ligand lipophilicity. The effects of ligand structure on gold nanoparticle attachment were further analyzed using atomistic molecular dynamics simulations, which showed that increasing ligand lipophilicity promotes ligand intercalation into the lipid bilayer. Together, the experimental and simulation results could be described by a two-state model that accounts for initial attachment and subsequent conversion to a quasi-irreversibly bound state. We find that only nanoparticles coated with the most lipophilic ligands in our nanoparticle library undergo conversion to the quasi-irreversible state. We propose that initial attachment is governed by interaction between the ligands and phospholipid tail groups, while conversion into the quasi-irreversibly bound state reflects ligand intercalation between phospholipid tail groups and eventual lipid extraction from the bilayer. Systematic variation of ligand lipophilicity enabled us to demonstrate that the lipophilicity of cationic ligands correlates with nanoparticle-bilayer adsorption and suggests that changing the nonpolar ligand R group promotes a mechanism of ligand intercalation into the bilayer associated with irreversible adsorption.
登录
查看更多内容
影响因子：
18.3
作者：
Kim, Sung Tae;Saha, Krishnendu;Kim, Chaekyu;Rotello, Vincent M.
通讯作者：
Rotello, Vincent M.
影响因子：
3
作者：
KUMAR, S;ROSENBERG, JM;KOLLMAN, PA
通讯作者：
KOLLMAN, PA
影响因子：
3.9
作者：
Liu, Xitong;Chen, Kai Loon
通讯作者：
Chen, Kai Loon
影响因子：
7.4
作者：
Haiss, Wolfgang;Thanh, Nguyen T. K.;Fernig, David G.
通讯作者：
Fernig, David G.
影响因子：
15
作者：
Moyano, Daniel F;Goldsmith, Meir;Solfiell, David J;Landesman-Milo, Dalit;Miranda, Oscar R;Peer, Dan;Rotello, Vincent M
通讯作者：
Rotello, Vincent M