Entrapment and Voltage-Driven Reorganization of Hydrophobic Nanoparticles in Planar Phospholipid Bilayers
Entrapment and Voltage-Driven Reorganization of Hydrophobic Nanoparticles in Planar Phospholipid Bilayers
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DOI：
10.1021/acsami.2c16677
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发表时间：
2022-12-14
影响因子：
9.5
通讯作者：
Spittle，Stephanie
中科院分区：
文献类型：
--
作者：
Basham，Colin M.;Sarles，Stephen A.;Spittle，Stephanie
工程纳米颗粒（NP）具有不同的物理和化学性质，这使它们成为人体内靶向细胞相互作用的有吸引力的试剂。一旦附着于质膜，NP可以嵌入其疏水核心内，这可以限制预期的治疗功能并影响相关的毒性。因此，理解嵌入的NP对质膜的物理作用对于理解它们的设计和临床用途至关重要。在这里，我们证明了功能化的，疏水性的金纳米颗粒溶解在油中，可以直接被困在使用液滴界面双层技术组装的磷脂膜的疏水内部。这种膜形成模型的方法保留了细胞膜中发现的侧向脂质扩散，并允许同时成像和电生理学研究嵌入的NP对双层机电性质的影响。我们发现，被困的纳米颗粒增强离子电导和侧膜张力在1，2-dioleoyl-sn-glycero-3-phosphocholine（DOPC）和1，2-diphytanoyl-sn-glycero-3-phosphocholine（DPhPC）双层，同时降低粘附能的加入液滴。嵌入的纳米颗粒也会引起双层电容和面积的变化，响应于所施加的电压，这是非单调的DOPC双层。这种电物理表征可以揭示NP截留，而不依赖于膜厚度的变化。通过评估所施加的电位下的膜张力的能量成分，我们证明了这些非单调的，电压依赖性的反应是由不饱和DOPC膜核内的NP的可逆聚类引起的;聚集体在低电压下自发形成，并通过与细胞环境中发现的那些类似的幅度的更高的跨膜电位分散。这些发现使人们能够更好地理解脂质依赖性NP相互作用，同时为研究其他疏水纳米材料与有机膜之间的关系提供了平台。
Engineered nanoparticles (NPs) possess diverse physical and chemical properties, which make them attractive agents for targeted cellular interactions within the human body. Once affiliated with the plasma membrane, NPs can become embedded within its hydrophobic core, which can limit the intended therapeutic functionality and affect the associated toxicity. As such, understanding the physical effects of embedded NPs on a plasma membrane is critical to understanding their design and clinical use. Here, we demonstrate that functionalized, hydrophobic gold NPs dissolved in oil can be directly trapped within the hydrophobic interior of a phospholipid membrane assembled using the droplet interface bilayer technique. This approach to model membrane formation preserves lateral lipid diffusion found in cell membranes and permits simultaneous imaging and electrophysiology to study the effects of embedded NPs on the electromechanical properties of the bilayer. We show that trapped NPs enhance ion conductance and lateral membrane tension in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) bilayers while lowering the adhesive energy of the joined droplets. Embedded NPs also cause changes in bilayer capacitance and area in response to applied voltage, which are nonmonotonic for DOPC bilayers. This electrophysical characterization can reveal NP entrapment without relying on changes in membrane thickness. By evaluating the energetic components of membrane tension under an applied potential, we demonstrate that these nonmonotonic, voltage-dependent responses are caused by reversible clustering of NPs within the unsaturated DOPC membrane core; aggregates form spontaneously at low voltages and are dispersed by higher transmembrane potentials of magnitude similar to those found in the cellular environment. These findings allow for a better understanding of lipid-dependent NP interactions, while providing a platform to study relationships between other hydrophobic nanomaterials and organic membranes.