Elucidating self-assembly processes based on the development of peptide atomic-resolution imaging

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K14704
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 34020:Analytical chemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Takayuki Nakamuro 東京大学, 総括プロジェクト機構, 特任准教授 (30831276)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: electron microscopy / peptide / single-molecule / self-assembly / atomic-resolution

Outline of Final Research Achievements

This report outlines the development and application of Single-Molecule Atomic Resolution Time-Resolved Electron Microscopy (SMART-EM) in the study of molecular dynamics in complex systems. I employed this innovative method to closely analyze the calcium-dependent self-assembly process of Daptomycin, a drug used to treat methicillin-resistant Staphylococcus aureus (MRSA). Additionally, the technique was applied to image N-alkyl peptides (peptoids), revealing that their rigid structures are maintained under vacuum conditions. Our findings suggest that SMART-EM is also applicable to imaging other flexible molecules and other peptides. This methodology opens new avenues for the structural characterization of molecules at the single-molecule level using transmission electron microscopy.

Free Research Field

電子顕微鏡学

Academic Significance and Societal Importance of the Research Achievements

自己集合現象は広範な科学分野での重要な研究テーマであり，本研究ではペプチド凝集挙動に着目した研究を進めた．ペプチド凝集挙動の解明は，物理的性質を理解するだけに留まらず機能性マテリアルへの合成応用など基礎から応用研究まで重要とされる．原子分解能イメージング法の開発によって単分子から凝集体に対する精緻な構造情報の取得が可能となった．本手法は，分子の剛直性や結合様式の理解を深めるだけでなく，得られた知見を創薬研究へ応用する道を拓くと期待される．