한빛사논문
- 조회1,440
M. T. Jeena,† Keunsoo Jeong,‡ Eun Min Go,§ Yuri Cho,‡,⊥ Seokyung Lee,‡ Seongeon Jin,† Suk-Won Hwang,⊥ Joo Hee Jang,# Chi Soo Kang,# Woo-Young Bang,∥ Eunji Lee,∥ Sang Kyu Kwak,*,§ Sehoon Kim,*,‡,⊥ and Ja-Hyoung Ryu*,†
† Department of Chemistry, School of Natural Science and §Department of Energy Engineering, School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Republic of Korea
‡ Center for Theragnosis, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
∥ School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju 61005, Republic of Korea
⊥ KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea
# Division of Applied RI, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea
Abstract
Self-assembly of peptides containing both l- and d-isomers often results in nanostructures with enhanced properties compared to their enantiomeric analogues, such as faster kinetics of formation, higher mechanical strength, and enzymatic stability. However, occurrence and consequences of the heterochiral assembly in the cellular microenvironment are unknown. In this study, we monitored heterochiral assembly of amphiphilic peptides inside the cell, specifically mitochondria of cancer cells, resulting in nanostructures with refined morphological and biological properties owing to the superior interaction between the backbones of opposite chirality. We have designed a mitochondria penetrating tripeptide containing a diphenyl alanine building unit, named as Mito-FF due to their mitochondria targeting ability. The short peptide amphiphile, Mito-FF co-assembled with its mirror pair, Mito-ff, induced superfibrils of around 100 nm in diameter and 0.5–1 μm in length, while enantiomers formed only narrow fibers of 10 nm in diameter. The co-administration of Mito-FF and Mito-ff in the cell induced drastic mitochondrial disruption both in vitro and in vivo. The experimental and theoretical analyses revealed that pyrene capping played a major role in inducing superfibril morphology upon the co-assembly of racemic peptides. This work shows the impact of chirality control over the peptide self-assembly inside the biological system, thus showing a potent strategy for fabricating promising peptide biomaterials by considering chirality as a design modality.
KEYWORDS : heterochiral assembly, intramitochondrial, supramolecular therapy, self-assembly
논문정보
- Research article
- 2019년 09월 (BRIC 등록일 2019-09-27)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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