ACS Nano. 2015;9(4):3704-20. doi: 10.1021/acsnano.5b01285. Epub 2015 Apr 9.
The adhesion and engulfment of nanoparticles by biomembranes is essential for many processes such as biomedical imaging, drug delivery, nanotoxicity, and viral infection. Many studies have shown that both surface chemistry, which determines the adhesive strength of the membrane-particle interactions, and particle size represent key parameters for these processes. Here, we show that the asymmetry between the two leaflets of a bilayer membrane provides another key parameter for the engulfment of nanoparticles. The asymmetric membrane prefers to curve in a certain manner as quantitatively described by its spontaneous curvature. We derive two general relationships between particle size, adhesive strength, and spontaneous curvature that determine the instabilities of (i) the nonadhering or free state and (ii) the completely engulfed state of the particle. For model membranes such as lipid or polymer bilayers with a uniform composition, the two relationships lead to two critical particle sizes that determine four distinct engulfment regimes, both for the endocytic and for the exocytic engulfment process. For strong adhesion, the critical particle sizes are on the order of 10 nm, while they are on the order of 1000 nm for weak or ultraweak adhesion. Our theoretical results are therefore accessible to both experimental studies and computer simulations of model membranes. In order to address the more complex process of receptor-mediated endocytosis, we take the adhesion-induced segregation of membrane components into account and consider bound and unbound membrane segments that differ in their spontaneous curvatures. To model protein coats as formed during clathrin-dependent endocytosis, we focus on the case in which the bound membrane segments have a large spontaneous curvature compared to the unbound ones. We derive explicit expressions for the engulfment rate and the uptake of nanoparticles, which both depend on the particle size in a nonmonotonic manner, and provide a quantitative fit to experimental data for clathrin-dependent endocytosis of gold nanoparticles.
生物膜对纳米颗粒的黏附和吞噬对于许多过程至关重要，如生物医学成像、药物传递、纳米毒性和病毒感染。许多研究表明，表面化学决定了膜-颗粒相互作用的黏附强度，颗粒大小则代表了这些过程的关键参数。在这里，我们表明双层膜的两个叶层之间的不对称性为纳米颗粒的吞噬提供了另一个关键参数。不对称膜倾向于以某种方式弯曲，这种弯曲可以通过其自发曲率来定量描述。我们推导出了两个一般关系，分别用于描述颗粒大小、黏附强度和自发曲率之间的关系，这些关系决定了颗粒的（i）非黏附或自由状态和（ii）完全吞噬状态的不稳定性。对于具有均匀组成的模型膜，如脂质或聚合物双层膜，这两个关系导致了两个决定四个不同吞噬状态的临界颗粒大小，这两种状态既适用于内吞作用，也适用于外排作用。对于强黏附，临界颗粒大小约为 10nm，而对于弱或超弱黏附，则约为 1000nm。因此，我们的理论结果既适用于实验研究，也适用于模型膜的计算机模拟。为了处理更复杂的受体介导内吞作用过程，我们考虑了膜成分的黏附诱导分离，并考虑了具有不同自发曲率的结合和未结合的膜段。为了模拟网格蛋白依赖性内吞作用过程中形成的蛋白质外壳，我们重点关注结合膜段的自发曲率与未结合膜段的自发曲率相比具有较大自发曲率的情况。我们推导出了吞噬率和纳米颗粒摄取的显式表达式，这两者都以非单调的方式依赖于颗粒大小，并对网格蛋白依赖性内吞作用的金纳米颗粒摄取实验数据提供了定量拟合。
