Bionanotechnology and Nanomedicine Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Biophys J. 2011 Dec 7;101(11):2693-703. doi: 10.1016/j.bpj.2011.09.059.
The polymorphism of eukaryotic cellular membranes is a tightly regulated and well-conserved phenotype. Recent data have revealed important regulatory roles of membrane curvature on the spatio-temporal localization of proteins and in membrane fusion. Here we quantified the influence of membrane curvature on the efficiency of intermembrane docking reactions. Using fluorescence microscopy, we monitored the docking of single vesicle-vesicle pairs of different diameter (30-200 nm) and therefore curvature, as mediated by neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and streptavidin-biotin. Surprisingly, the intermembrane docking efficiency exhibited an ∼30-60 fold enhancement as a function of curvature. In comparison, synaptotagmin and calcium accelerate SNARE-mediated fusion in vitro by a factor of 2-10. To explain this finding, we formulated a biophysical model. On the basis of our findings, we propose that membrane curvature can regulate intermembrane tethering reactions and consequently any downstream process, including the fusion of vesicles and possibly viruses with their target membranes.
真核细胞的细胞膜的多态性是一种受到严格调控和高度保守的表型。最近的数据揭示了膜曲率在蛋白质的时空定位和膜融合中的重要调节作用。在这里，我们量化了膜曲率对膜间对接反应效率的影响。我们使用荧光显微镜监测了由神经元可溶性 N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）和链霉亲和素-生物素介导的不同直径（30-200nm）和曲率的单囊泡-囊泡对的对接。令人惊讶的是，作为曲率的函数，膜间对接效率表现出约 30-60 倍的增强。相比之下，突触结合蛋白和钙在体外通过 2-10 倍的因子加速 SNARE 介导的融合。为了解释这一发现，我们提出了一个生物物理模型。基于我们的发现，我们提出膜曲率可以调节膜间系链反应，从而调节包括囊泡融合和可能的病毒与靶膜融合在内的任何下游过程。
