Mitochondria localization induced self-assembly of peptide amphiphiles for cellular dysfunction

M. T. Jeena, L. Palanikumar, Eun Min Go, Inhye Kim, Myoung Gyun Kang, Seonik Lee, Sooham Park, Huyeon Choi, Chaekyu Kim, Seon-Mi Jin, Sung Chul Bae, Hyun Woo Rhee, Eunji Lee (), Sang Kyu Kwak () and Ja-Hyoung Ryu ()
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M. T. Jeena: Ulsan National Institute of Science and Technology (UNIST)
L. Palanikumar: Ulsan National Institute of Science and Technology (UNIST)
Eun Min Go: Ulsan National Institute of Science and Technology (UNIST)
Inhye Kim: Chungnam National University
Myoung Gyun Kang: Ulsan National Institute of Science and Technology (UNIST)
Seonik Lee: Ulsan National Institute of Science and Technology (UNIST)
Sooham Park: Ulsan National Institute of Science and Technology (UNIST)
Huyeon Choi: Ulsan National Institute of Science and Technology (UNIST)
Chaekyu Kim: Ulsan National Institute of Science and Technology (UNIST)
Seon-Mi Jin: Chungnam National University
Sung Chul Bae: Ulsan National Institute of Science and Technology (UNIST)
Hyun Woo Rhee: Ulsan National Institute of Science and Technology (UNIST)
Eunji Lee: Chungnam National University
Sang Kyu Kwak: Ulsan National Institute of Science and Technology (UNIST)
Ja-Hyoung Ryu: Ulsan National Institute of Science and Technology (UNIST)

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00047-z

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