Inorganic nanoparticles (NPs) represent promising examples of engineered nanomaterials, providing interesting biomedical solutions in several fields, like therapeutics and diagnostics. Despite the extensive number of investigations motivated by their remarkable potential for nanomedicinal applications, the interactions of NPs with biological interfaces are still poorly understood. The effect of NPs on living organisms is mediated by biological barriers, such as the cell plasma membrane, whose lateral heterogeneity is thought to play a prominent role in NPs adsorption and uptake pathways. In particular, biological membranes feature the presence of rafts, that is segregated lipid micro and/or nanodomains in the so‐called liquid ordered phase (Lo), immiscible with the surrounding liquid disordered phase (Ld). Rafts are involved in various biological functions and act as sites for the selective adsorption of materials on the membrane. Indeed, the thickness mismatch present along their boundaries generates energetically favourable conditions for the adsorption of NPs. Despite its clear implications in NPs internalisation processes and cytotoxicity, a direct proof of the selective adsorption of NPs along the rafts’ boundaries is still missing to date. Here we use multicomponent supported lipid bilayers (SLBs) as reliable synthetic models, reproducing the nanometric lateral heterogeneity of cell membranes. After being characterised by atomic force microscopy (AFM) and neutron reflectivity (NR), multidomain SLBs are challenged by prototypical inorganic nanoparticles, that is citrated gold nanoparticles (AuNPs), under simplified and highly controlled conditions. By exploiting AFM, we demonstrate that AuNPs preferentially target lipid phase boundaries as adsorption sites. The herein reported study consolidates and extends the fundamental knowledge on NPs–membrane interactions, which constitute a key aspect to consider when designing NPs‐related biomedical applications.

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金纳米粒子与合成脂筏相互作用：AFM 研究

无机纳米粒子 (NP) 是工程纳米材料的有前途的例子，在治疗学和诊断学等多个领域提供了有趣的生物医学解决方案。尽管由于纳米医学应用的显着潜力而进行了大量研究，但对 NPs 与生物界面的相互作用仍然知之甚少。NPs 对生物体的影响是由生物屏障介导的，例如细胞质膜，其横向异质性被认为在 NPs 吸附和摄取途径中起重要作用。特别是，生物膜的特点是存在筏，即所谓的液体有序相（Lo）中分离的脂质微区和/或纳米区，与周围的液体无序相（Ld）不混溶。筏参与各种生物功能，并充当材料在膜上选择性吸附的位点。事实上，沿其边界存在的厚度不匹配为纳米颗粒的吸附产生了有利的条件。尽管它对 NPs 内化过程和细胞毒性有明显的影响，但迄今为止仍然缺少 NPs 沿筏边界选择性吸附的直接证据。在这里，我们使用多组分支持的脂质双层 (SLB) 作为可靠的合成模型，再现细胞膜的纳米横向异质性。在通过原子力显微镜 (AFM) 和中子反射率 (NR) 进行表征后，多域 SLB 受到原型无机纳米粒子的挑战，即柠檬酸金纳米粒子 (AuNPs)，在简化和高度控制的条件下。通过利用 AFM，我们证明 AuNPs 优先将脂质相边界作为吸附位点。本文报道的研究巩固并扩展了 NPs-膜相互作用的基础知识，这是设计 NPs 相关生物医学应用时需要考虑的一个关键方面。