Abstract:
Some antimicrobial peptides (AMPs) and membrane fusion-catalyzing peptides (FPs) stabilize bicontinuous inverted cubic (QII) phases. Previous authors proposed a topological rationale: since AMP-induced pores, fusion intermediates, and QII phases all have negative Gaussian curvature (NGC), peptides which produce NGC in one structure also do it in another. This assumes that peptides change the curvature energy of the lipid membranes. Here I test this with a Helfrich curvature energy model. First, experimentally, I show that lipid systems often used to study peptide NGC have NGC without peptides at higher temperatures. To determine the net effect of an AMP on NGC, the equilibrium phase behavior of the host lipids must be determined. Second, the model shows that AMPs must make large changes in the curvature energy to stabilize AMP-induced pores. Peptide-induced changes in elastic constants affect pores and QII phase differently. Changes in spontaneous curvature affect them in opposite ways. The observed correlation between QII phase stabilization and AMP activity doesn\'t show that AMPs act by lowering pore curvature energy. A different rationale is proposed. In theory, AMPs could simultaneously stabilize QII phase and pores by drastically changing two particular elastic constants. This could be tested by measuring AMP effects on the individual constants. I propose experiments to do that. Unlike AMPs, FPs must make only small changes in the curvature energy to catalyze fusion. It they act in this way, their fusion activity should correlate with their ability to stabilize QII phases.
摘要:
一些抗微生物肽(AMP)和膜融合催化肽(FP)稳定双连续倒立方(QII)相。以前的作者提出了一个拓扑原理:由于AMP诱导的毛孔,融合中间体,和QII阶段都具有负高斯曲率(NGC),在一种结构中产生NGC的肽也在另一种结构中产生NGC。这假定肽改变脂质膜的曲率能。在这里,我用Helfrich曲率能量模型进行测试。首先,实验,我显示经常用于研究肽NGC的脂质系统在较高温度下具有没有肽的NGC。为了确定AMP对NGC的净影响,必须确定宿主脂质的平衡相行为。第二,模型表明,AMP必须使曲率能量发生较大变化,以稳定AMP诱导的孔。肽诱导的弹性常数变化对孔隙和QII相的影响不同。自发曲率的变化以相反的方式影响它们。观察到的QII相稳定与AMP活性之间的相关性并未表明AMP通过降低孔隙曲率能而起作用。提出了不同的理由。理论上,AMP可以通过急剧改变两个特定的弹性常数来同时稳定QII相和孔。这可以通过测量AMP对各个常数的影响来测试。我提出实验来做到这一点。与AMP不同,FP必须仅对曲率能量进行很小的改变以催化聚变。如果他们以这种方式行事,它们的融合活性应与它们稳定QII阶段的能力相关。