Membrane tension evolution and mechanical regulation of melittin-induced membrane poration

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外文摘要：Membrane tension plays a crucial role in various fundamental cellular processes,with one notable example being the T cell-mediated elimination of tumor cells through perforin-induced membrane perforation by amplifying cellular force.However,the mechanisms governing the regulation of biomolecular activities at the cell interface by membrane tension remain elusive.In this study,we investigated the correlation between membrane tension and poration activity of melittin,a prototypical pore-forming peptide,using dynamic giant unilamellar vesicle leakage assays combined with flickering ten-sion analysis,molecular dynamics simulations,and live cell assays.The results demonstrate that an increase in membrane tension enhances the activity of melittin,particularly near its critical pore-forming concentration.Moreover,peptide actions such as binding,insertion,and aggregation in the membrane further influence the evolution of membrane tension.Live cell experiments reveal that artificially enhancing membrane tension effectively enhances melittin's ability to induce pore for-mation and disrupt membranes,resulting in up to a ten-fold increase in A549 cell mortality when exposed to a concentration of 2.0-μg·mL-1 melittin.Our findings elucidate the relationship between membrane tension and the mechanism of action as well as pore-forming efficiency of melittin,while providing a practical mechanical approach for regulating functional activity of molecules at the cell-membrane interface.

外文关键词：

membrane tensionmechanical regulationmembrane porationgiant unilamellar vesicle leakage assay

作者：

张婉婷、徐榕、马文东、林召、杨恺、元冰

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作者单位：

Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical Science and Technology,Soochow University,Suzhou 215006,China

Songshan Lake Materials Laboratory,Dongguan 523808,China

Biomedicine Discovery Institute,Infection & Immunity Program,Monash University,Melbourne,Australia

Beijing National Laboratory for Condensed Matter Physics,Institute of Physics,Chinese Academy of Sciences,Beijing 100190,China

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基金：

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaBasic and Applied Basic Research Foundation of Guangdong Province,China

项目编号：

122743073223006321774092123471022023A1515011610

出版年：

2024

DOI：

10.1088/1674-1056/ad6254

中国物理B(英文版)

中国物理学会和中国科学院物理研究所

中国物理B(英文版)

CSTPCDEI

影响因子：0.995

ISSN：1674-1056

年,卷(期)：2024.33(10)