Statistical analysis of peptide-induced graded and all-or-none fluxes in giant vesicles.
Statistical analysis of peptide-induced graded and all-or-none fluxes in giant vesicles.
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DOI：
10.1016/j.bpj.2013.05.055
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发表时间：
2013-07
影响因子：
3.4
通讯作者：
Sterling A. Wheaten;A. Lakshmanan;P. Almeida
中科院分区：
文献类型：
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作者：
Sterling A. Wheaten;A. Lakshmanan;P. Almeida
抗微生物、细胞溶解和细胞穿透肽诱导磷脂膜中的孔或扰动，导致染料流入或流出脂质囊泡。在这里，我们研究这些膜活性肽在巨大的单层囊泡中诱导的通量。通量的类型是从作为其染料含量的函数的囊泡的分布的模态使用统计的Hartigan浸渍测试确定的。分级和全或无通量分别对应于单峰和双峰分布。为了了解这些分布是如何产生的，我们使用一个非常简单的模型进行蒙特卡罗模拟肽诱导的染料通量进入囊泡。分布的形态取决于孔的打开和关闭的速率常数，和染料通量。如果孔的打开和关闭速率常数都远小于染料通过孔的速率常数，则发生全或无内流。然而，如果其中之一，特别是孔隙开放的速率常数，相对于通量速率常数显着增加，该过程变得分级。在实验中，我们发现，流量类型是相同的，在巨大的囊泡，所有的肽，除了一个。但这一例外表明通量类型不能用于明确预测肽的膜透化机制。
Antimicrobial, cytolytic, and cell-penetrating peptides induce pores or perturbations in phospholipid membranes that result in fluxes of dyes into or out of lipid vesicles. Here we examine the fluxes induced by four of these membrane-active peptides in giant unilamellar vesicles. The type of flux is determined from the modality of the distributions of vesicles as a function of their dye content using the statistical Hartigan dip test. Graded and all-or-none fluxes correspond to unimodal and bimodal distributions, respectively. To understand how these distributions arise, we perform Monte Carlo simulations of peptide-induced dye flux into vesicles using a very simple model. The modality of the distributions depends on the rate constants of pore opening and closing, and dye flux. If the rate constants of pore opening and closing are both much smaller than that of dye flux through the pore, all-or-none influx occurs. However, if one of them, especially the rate constant for pore opening, increases significantly relative to the flux rate constant, the process becomes graded. In the experiments, we find that the flux type is the same in giant and large vesicles, for all peptides except one. But this one exception indicates that the flux type cannot be used to unambiguously predict the mechanism of membrane permeabilization by the peptides.