Fabrication of cytotoxic mirror image nanopores.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-02 DOI:10.1038/s41467-025-64025-6

Neilah Firzan Ca,Kalyanashis Jana,Sreelakshmi Radhakrishnan,Rifat Aara,Mubeena S,Radhika Nair,Harsha Bajaj,Ulrich Kleinekathöfer,Kozhinjampara R Mahendran

{"title":"Fabrication of cytotoxic mirror image nanopores.","authors":"Neilah Firzan Ca,Kalyanashis Jana,Sreelakshmi Radhakrishnan,Rifat Aara,Mubeena S,Radhika Nair,Harsha Bajaj,Ulrich Kleinekathöfer,Kozhinjampara R Mahendran","doi":"10.1038/s41467-025-64025-6","DOIUrl":null,"url":null,"abstract":"Synthetic nanopores composed of mirror-image peptides have been reported, but not fully functional mirror-image pores. Here, we construct a monodisperse mirror-image nanopore, DpPorA and characterise its functional properties. Importantly, we alter the charge pattern and assemble a superior mirror-image pore with enhanced conductance and selectivity under different salt conditions. This pore is used for single-molecule sensing of structurally divergent biomolecules, including peptides, PEGylated polypeptides, full-length alpha-synuclein protein and cyclic sugars. Molecular dynamics simulations confirm these DpPorA are exact mirror-images of LpPorA, further revealing their structurally stable conformation. Fluorescence imaging of giant vesicles reconstituted with mirror-image peptides reveals the formation of large flexible pores facilitating size-dependent molecular transport. To explore biomedical applications, the differential cytotoxic effect of mirror-image peptides and their fluorescently tagged forms on cancer cells demonstrates a significant effect on membrane disruption and cell viability, as opposed to no effect on normal cells. We emphasize that this class of mirror-image pores can advance the development of molecular sensors and therapeutics.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"62 1","pages":"8666"},"PeriodicalIF":15.7000,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-64025-6","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Synthetic nanopores composed of mirror-image peptides have been reported, but not fully functional mirror-image pores. Here, we construct a monodisperse mirror-image nanopore, DpPorA and characterise its functional properties. Importantly, we alter the charge pattern and assemble a superior mirror-image pore with enhanced conductance and selectivity under different salt conditions. This pore is used for single-molecule sensing of structurally divergent biomolecules, including peptides, PEGylated polypeptides, full-length alpha-synuclein protein and cyclic sugars. Molecular dynamics simulations confirm these DpPorA are exact mirror-images of LpPorA, further revealing their structurally stable conformation. Fluorescence imaging of giant vesicles reconstituted with mirror-image peptides reveals the formation of large flexible pores facilitating size-dependent molecular transport. To explore biomedical applications, the differential cytotoxic effect of mirror-image peptides and their fluorescently tagged forms on cancer cells demonstrates a significant effect on membrane disruption and cell viability, as opposed to no effect on normal cells. We emphasize that this class of mirror-image pores can advance the development of molecular sensors and therapeutics.

查看原文本刊更多论文

细胞毒性镜像纳米孔的制备。

镜像肽的合成纳米孔已被报道，但没有完全功能的镜像孔。在这里，我们构建了一个单分散镜像纳米孔DpPorA，并表征了它的功能特性。重要的是，我们改变了电荷模式，并在不同的盐条件下组装了具有增强电导率和选择性的优越镜像孔。该孔用于结构上不同的生物分子的单分子传感，包括多肽、聚乙二醇化多肽、全长α -突触核蛋白和环糖。分子动力学模拟证实了这些DpPorA是LpPorA的精确镜像，进一步揭示了它们结构稳定的构象。用镜像肽重建的巨囊泡的荧光成像显示，形成了大的柔性孔隙，促进了大小依赖的分子运输。为了探索生物医学应用，镜像肽及其荧光标记形式对癌细胞的差异细胞毒性作用表明，与对正常细胞没有影响相反，镜像肽对细胞膜破坏和细胞活力有显著影响。我们强调，这类镜像孔可以促进分子传感器和治疗的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.