Deciphering How Pore Formation Causes Strain-Induced Membrane Lysis of Lipid Vesicles

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• 作者：Joshua A. Jackman ; Haw Zan Goh ; Vladimir P. Zhdanov ; Wolfgang Knoll ; Nam-Joon Cho
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：February 3, 2016
• 年：2016
• 卷：138
• 期：4
• 页码：1406-1413
• 全文大小：522K
• ISSN：1520-5126

文摘

Pore formation by membrane-active antimicrobial peptides is a classic strategy of pathogen inactivation through disruption of membrane biochemical gradients. It remains unknown why some membrane-active peptides also inhibit enveloped viruses, which do not depend on biochemical gradients. Here, we employ a label-free biosensing approach based on simultaneous quartz crystal microbalance-dissipation and ellipsometry measurements in order to investigate how a pore-forming, virucidal peptide destabilizes lipid vesicles in a surface-based experimental configuration. A key advantage of the approach is that it enables direct kinetic measurement of the surface-bound peptide-to-lipid (P:L) ratio. Comprehensive experiments involving different bulk peptide concentrations and biologically relevant membrane compositions support a unified model that membrane lysis occurs at or above a critical P:L ratio, which is at least several-fold greater than the value corresponding to the onset of pore formation. That is consistent with peptide-induced pores causing additional membrane strain that leads to lysis of highly curved membranes. Collectively, the work presents a new model that describes how peptide-induced pores may destabilize lipid membranes through a membrane strain-related lytic process, and this knowledge has important implications for the design and application of membrane-active peptides.