Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina, USA.
Biophys J. 2013 Jul 16;105(2):432-43. doi: 10.1016/j.bpj.2013.05.055.
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.
抗菌、溶细胞和细胞穿透肽在磷脂膜中诱导孔或扰动，导致染料流入或流出脂质体。在这里，我们研究了这四种膜活性肽在巨大单层囊泡中诱导的通量。通量的类型是通过使用统计哈特igan 双测试，根据囊泡的染料含量与其分布模式来确定的。分级和全有或全无通量分别对应于单峰和双峰分布。为了理解这些分布是如何产生的，我们使用一个非常简单的模型对肽诱导染料进入囊泡的通量进行了蒙特卡罗模拟。分布的模态取决于孔的开启和关闭的速率常数，以及染料的通量。如果孔的开启和关闭的速率常数都远小于染料通过孔的通量常数，那么全有或全无的流入就会发生。然而，如果其中一个速率常数，特别是孔的开启速率常数，相对于通量速率常数显著增加，那么这个过程就会变成分级的。在实验中，我们发现除了一种肽之外，所有肽在巨大囊泡和大囊泡中的通量类型都是相同的。但这个例外表明，通量类型不能用于明确预测肽对膜通透性的作用机制。
