Jeena M T, Palanikumar L, Go Eun Min, Kim Inhye, Kang Myoung Gyun, Lee Seonik, Park Sooham, Choi Huyeon, Kim Chaekyu, Jin Seon-Mi, Bae Sung Chul, Rhee Hyun Woo, Lee Eunji, Kwak Sang Kyu, Ryu Ja-Hyoung
Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
Nat Commun. 2017 Jun 21;8(1):26. doi: 10.1038/s41467-017-00047-z.
Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy. The Mito-FF fibrils induce mitochondrial dysfunction via membrane disruption to cause apoptosis. The organelle-specific supramolecular system provides a new opportunity for therapeutics and in-depth investigations of cellular functions.Spatiotemporal control of intracellular molecular self-assembly holds promise for therapeutic applications. Here the authors develop a peptide consisting of a phenylalanine dipeptide with a mitochondrial targeting moiety to form self-assembling fibrous nanostructures within mitochondria, leading to apoptosis.
由于细胞环境的复杂性和缺乏表征工具，实现与活细胞内生物功能激活相关的分子自组装的时空控制仍然是一项挑战。我们首次展示了肽两亲分子的细胞器定位自组装，这是一种控制细胞命运的强大策略。带有线粒体靶向基团三苯基膦的苯丙氨酸二肽（Mito-FF）优先在线粒体内积累，并达到临界聚集浓度以形成纤维状纳米结构，通过共聚焦激光扫描显微镜和透射电子显微镜对其进行监测。Mito-FF 纤维通过膜破坏诱导线粒体功能障碍，从而导致细胞凋亡。这种细胞器特异性超分子系统为治疗和深入研究细胞功能提供了新机会。细胞内分子自组装的时空控制在治疗应用方面具有前景。本文作者开发了一种由带有线粒体靶向基团的苯丙氨酸二肽组成的肽，以在线粒体内形成自组装纤维状纳米结构，从而导致细胞凋亡。
