Critical Particle Sizes for the Engulfment of Nanoparticles by Membranes and Vesicles with Bilayer Asymmetry
Critical Particle Sizes for the Engulfment of Nanoparticles by Membranes and Vesicles with Bilayer Asymmetry
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DOI：
10.1021/acsnano.5b01285
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发表时间：
2015-04-01
期刊：
影响因子：
17.1
通讯作者：
Lipowsky, Reinhard
中科院分区：
文献类型：
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作者：
Agudo-Canalejo, Jaime;Lipowsky, Reinhard
生物膜对纳米粒子的粘附和吞噬对于生物医学成像、药物递送、纳米毒性和病毒感染等许多过程是必不可少的。许多研究表明，表面化学（决定膜-颗粒相互作用的粘附强度）和粒度都是这些过程的关键参数。在这里，我们表明，双层膜的两个小叶之间的不对称性提供了另一个关键参数的纳米粒子的吞噬。非对称膜倾向于以某种方式弯曲，如其自发曲率所定量描述的。我们推导出两个一般的颗粒大小，粘附强度和自发曲率之间的关系，确定的不稳定性（i）的非粘附或自由状态和（ii）的完全吞没状态的颗粒。对于模型膜，如具有均匀组成的脂质或聚合物双层，这两种关系导致两个临界颗粒尺寸，其确定四种不同的吞噬制度，无论是内吞还是外吞吞噬过程。对于强粘附力，临界颗粒尺寸为10 nm的数量级，而对于弱粘附力或超弱粘附力，临界颗粒尺寸为1000 nm的数量级。因此，我们的理论结果可以用于模型膜的实验研究和计算机模拟。为了解决受体介导的内吞作用的更复杂的过程中，我们考虑到膜组件的粘附诱导的隔离，并考虑绑定和未绑定的膜段，其自发曲率不同。为了模拟网格蛋白依赖的内吞作用过程中形成的蛋白质涂层，我们专注于结合膜段的情况下，有一个大的自发曲率相比，未结合的。我们推导出明确的表达式的吞噬率和纳米颗粒的摄取，这两者都依赖于在一个非单调的方式的颗粒大小，并提供了一个定量拟合的实验数据网格蛋白依赖的内吞作用的金纳米颗粒。
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 nnn 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.