乐世敏  

代表性文章或专著：

一、通讯（共同通讯）作者文章（*）：

[1]. Y. Wang, J. Ye, X. Liu, Z. Zhang, F. Shang, X. Qi, Y. Zhang, J. Du, H. Sun, J. Xu, H. Chen*, M. Yu*, S. Le*, Mechanically weak and highly dynamic state of mechanosensitive titin Ig domains induced by proline isomerization, Nature Communications 16(1):2771(2025)

[2]. Y. Zhang, Z. Zhang, H. Sun, Z. Xue, Y. Wang, Z. Guo, S. Le*, & H. Chen*, Anomalous Force-Dependent Transition Rates Unveil Dual Pathways in Folding and Unfolding Dynamics of Acyl-coenzyme A Binding Protein, The Journal of Physical Chemistry Letters 16, 2479-2486 (2025)

[3]. Y. Zhang#, J. Du#, X. Liu, F. Shang, Y. Deng, J. Ye, Y. Wang, J.Yan, H. Chen*, M. Yu* & S. Le*, Multi-domain interaction mediated strength-building in human α-actinin dimers unveiled by direct single-molecule quantification, Nature Communications 15: 6151 (2024)

[4]. J. Xu, H. Sun, Z. Zhang, Z. Guo, S. Le*, H. Chen* , Folding and Misfolding Dynamics of Irisin Protein Revealed by Single-Molecule Magnetic Tweezers  , The Journal of Physical Chemistry Letters 15, 11954-11960 (2024)

[5]. Z Xue, H Sun, H Hong, Z Zhang, Y Zhang, Z Guo,  S. Le*, H Chen*, Comparative analysis of folding and unfolding dynamics and free-energy landscapes in homologous cold shock proteins with variable thermal stabilities, Physical Review Research 6 (2), 023170 (2024)

[6]. M. Yu, J. Lu, S. Le*, and J. Yan*, Unexpected Low Mechanical Stability of Titin I27 Domain at Physiologically Relevant Temperature, The Journal of Physical Chemistry Letters 12(33), 7914-7920 (2021)
[7]. M. Yu, Z. Zhao, Z. Chen, S. Le*, and J. Yan*, Modulating Mechanical Stability of Heterodimerization Between Engineered Orthogonal Helical Domains, Nature Communications 11: 4476 (2020)

二、第一（共同第一）作者文章（#）：

[1]. S. Le#, M. Yu#, C. Fu#, JA Heier, S Martin, J. Hardin*, J. Yan* , Single-molecule force spectroscopy reveals intra- and intermolecular interactions of Caenorhabditis elegans HMP-1 during mechanotransduction, Proceedings of the National Academy of Sciences 121 (37), e2400654121 (2024)

[2]. M. Yu#, S. Le#, S. Barnett#, Z. Guo, X. Zhong, P. Kanchanawong*, and J. Yan*,  Implementing Optogenetic Modulation in Mechanotransduction, Physical Review X 10, 021001 (2020)
[3]. S. Le#, M. Yu#, and J. Yan*, Direct Single-molecule Quantification Reveals Surprisingly High Mechanical Stability of Vinculin--Talin/alpha-Catenin Linkages, Science Advances 5 (12), eaav2720 (2019)
[4]. S. Le#, M. Yu#, and J. Yan*, Phosphorylation Reduces the Mechanical Stability of alpha-catenin/beta-catenin Complex, Angewandte Chemie International Edition 58(51) 18663-18669 (2019)
[5]. M. Yu#, S. Le#, Y. Ammon#, B. Goult, A. Akhmanova*, and J. Yan*, Force-dependent Regulation of KANK1-talin Complex at Focal Adhesions, Nano Letters 19 (9), 5982-5990 (2019)
[6]. S. Le, M. Yu, L. Hovan, Z. Zhao, J. Ervasti, and J. Yan*, Dystrophin as a Molecular Shock Absorber, ACS Nano 12(12):12140-12148 (2018)
[7]. M. Yu#, S. Le#, A. Efremov, X. Zeng, A. Bershadsky, and J. Yan*, Effects of Mechanical Stimuli on Profilin- and Formin-mediated Actin Polymerization, Nano Letters 18 (8), 5239-5247. (2018)
[8]. S. Le, X. Hu, M. Yao, H. Chen, M. Yu, X. Xu, F. Margadant, M. Sheetz*, and J. Yan*, Mechanotransmission and Mechanosensing of Human alpha-actinin 1, Cell Reports 21, 1-10. (2017)
[9]. S. Le#, E. Serrano#, R. Kawamura B. Carrasco, J. Yan*, and J.Alonso*, Bacillus Subtilis DprA and SsbA Promote the Assembly of a RecA Nucleoprotein Filament that Can Overcome RecX Inhibition during Natural Chromosomal Transformation, Nucleic Acids Research 45(15): 8873-8885 (2017)
[10]. S. Le#, M. Yao#, J. Chen, A. K. Efremov, S. Azimi, and J. Yan*, Disturbance-free Rapid Solution Exchange for Magnetic Tweezers Single-molecule Studies, Nucleic Acids Research 43(17): e113 (2015)
[11]. S. Le, H. Chen, X. Zhang, J. Chen, K. Patil, K. Muniyappa*, and J. Yan*, Mechanical Force Antagonizes the Inhibitory Effects of RecX on RecA Filaments Formation in M. tuberculosis, Nucleic Acids Research 42 (19): 11992-11999. (2014)
[12]. H. Fu#, S. Le#, H. Chen, K. Muniyappa*, and J. Yan*, Force and ATP Hydrolysis Dependent Regulation of RecA Nucleoprotein Filament by Single-stranded DNA Binding Protein, Nucleic Acids Research 41, 924 (2013)

三、综述文章：

[1]. S. Le, M. Yu, A. Bershadsky*, and J.Yan*, Mechanical regulation of formin-dependent actin polymerization. Seminars In Cell & Developmental Biology 102: 73-80 (2020).
[2]. S. Le, M. Yu, and J. Yan*, Mechanical Regulation of Tension-transmission Supramolecular Linkages, Current Opinion in Solid State and Materials Science 25:100895 (2021).

力学生物学 (Mechanobiology) 是生物、物理、医学、工程等多学科交叉发展的新兴前沿研究方向。

近年研究表明细胞黏附、迁移与分化，组织生长、修复与维持，胚胎发育，肿瘤生长与转移，免疫应答，衰老等一系列重要的生理、病理过程都受到力信号的调控。力学生物学研究旨在研究力信号对生命体在分子、亚细胞、细胞、组织、器官等层次行为的调控机制，及在机制理解与指导下的生物医学应用。其分子基础是一系列力敏感的生物大分子（蛋白质、核酸等）及其介导的力敏感信号通路的力学响应与调控。

课题组以探究生命医学重要问题为目标，聚焦“生物大分子动态与互作的力学调控机制”及其潜在生物医学应用，注重物理与生物、医学交叉，致力于通过单分子、单细胞力学操控与成像等技术，揭示关键生理、病理过程中的蛋白质构象、修饰、蛋白质—蛋白质互作、核酸—蛋白质互作在生理范围力作用下力学-化学-生物耦合动态调控的分子机制。 在机制理解与指导下，开展新型力敏感蛋白通路干预分子、多肽、蛋白等潜在药物的开发与转化应用，推进力医学(Mechanomedicine) 发展。

课题组当前之课题方向简述：

1). 细胞黏附、胞间连接关键力敏感蛋白质，及其介导的力敏感信号通路力学-化学-生物耦合调控机制的单分子与单细胞研究；

2). 细胞骨架与细胞核骨架关键力敏感蛋白质，及其介导的力敏感信号通路力学-化学-生物耦合调控机制的单分子与单细胞研究；

3). 肌联蛋白（Titin）的构象（去折叠、复折叠、错误折叠、中间态等）、修饰（氧化、异构、磷酸化等）、互作（信号蛋白、分子伴侣等）的力学-化学-生物耦合调控机制研究；

4). 活细胞内力学、化学、生物信号的原位探测技术开发与应用；

5). 干预、调控蛋白质分子的AI辅助从头设计、优化与应用；