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| 1 | Liquid-liquid phase separation in biology: mechanisms,physiological functions and human diseases显示文摘Cells are compartmentalized by numerous membrane-enclosed organelles and membraneless compartments to ensure that a wide variety of cellular activities occur in a spatially and temporally controlled manner. The molecular mechanisms underlying the dynamics of membrane-bound organelles, such as their fusion and fission, vesicle-mediated trafficking and membrane contactmediated inter-organelle interactions, have been extensively characterized. However, the molecular details of the assembly and functions of membraneless compartments remain elusive. Mounting evidence has emerged recently that a large number of membraneless compartments, collectively called biomacromolecular condensates, are assembled via liquid-liquid phase separation(LLPS). Phase-separated condensates participate in various biological activities, including higher-order chromatin organization,gene expression, triage of misfolded or unwanted proteins for autophagic degradation, assembly of signaling clusters and actin-and microtubule-based cytoskeletal networks, asymmetric segregations of cell fate determinants and formation of pre-and post-synaptic density signaling assemblies. Biomacromolecular condensates can transition into different material states such as gel-like structures and solid aggregates. The material properties of condensates are crucial for fulfilment of their distinct functions, such as biochemical reaction centers, signaling hubs and supporting architectures. Cells have evolved multiple mechanisms to ensure that biomacromolecular condensates are assembled and disassembled in a tightly controlled manner. Aberrant phase separation and transition are causatively associated with a variety of human diseases such as neurodegenerative diseases and cancers. This review summarizes recent major progress in elucidating the roles of LLPS in various biological pathways and diseases. | Hong Zhang Xiong Ji Pilong Li Cong Liu Jizhong Lou Zheng Wang Wenyu Wen Yue Xiao Mingjie Zhang Xueliang Zhu | 2020 | Science China(Life Sciences)2020，63，7： | 11 |
| 2 | Liquid-liquid phase separation by SARS-CoV-2 nucleocapsid protein and RNA显示文摘Dear Editor,The COVID-19 pandemic worldwide is caused by a novel coronavirus SARS-CoV-2(the severe acute respiratory syndrome coronavirus 2).1 After viral invasion into the host cells,the〜30 kb viral genome RNA injected is translated into structural and nonstructural proteins to replicate viral genome and assemble more viral particles.Many copies of nucleocapsid(N)protein can bind to viral genome RNA and pack it into^100 nm particles,assisting membrane(M)and envelope(E)proteins to efficiently assemble the viral envelope.2 The exact molecular mechanism by which N protein packs up the viral genome still remains elusive. | Hui Chen Yang Cui Xuling Han Wei Hu Min Sun Yong Zhang Pei-Hui Wang Guangtao Song Wei Chen Jizhong Lou | 2020 | Cell Research2020，30，12： | 3 |
| 3 | Mechanical activation of spike fosters SARS-CoV-2 viral infection显示文摘The outbreak of SARS-CoV-2(SARS2)has caused a global COVID-19 pandemic.The spike protein of SARS2(SARS2-S)recognizes host receptors,including ACE2,to initiate viral entry in a complex biomechanical environment.Here,we reveal that tensile force,generated by bending of the host cell membrane,strengthens spike recognition of ACE2 and accelerates the detachment of spike’s S1 subunit from the S2 subunit to rapidly prime the viral fusion machinery.Mechanistically,such mechano-activation is fulfilled by force-induced opening and rotation of spike’s receptor-binding domain to prolong the bond lifetime of spike/ACE2 binding,up to 4 times longer than that of SARS-S binding with ACE2 under 10 pN force application,and subsequently by force-accelerated S1/S2 detachment which is up to~103 times faster than that in the no-force condition.Interestingly,the SARS2-S D614G mutant,a more infectious variant,shows 3-time stronger force-dependent ACE2 binding and 35-time faster force-induced S1/S2 detachment.We also reveal that an anti-S1/S2 non-RBD-blocking antibody that was derived from convalescent COVID-19 patients with potent neutralizing capability can reduce S1/S2 detachment by 3×106 times under force.Our study sheds light on the mechano-chemistry of spike activation and on developing a non-RBD-blocking but S1/S2-locking therapeutic strategy to prevent SARS2 invasion. | Wei Hu Yong Zhang Panyu Fei Tongtong Zhang Danmei Yao Yufei Gao Jia Liu Hui Chen Qiao Lu Tenny Mudianto Xinrui Zhang Chuxuan Xiao Yang Ye Qiming Sun Jing Zhang Qi Xie Pei-Hui Wang Jun Wang Zhenhai Li Jizhong Lou Wei Chen | 2021 | Cell Research2021，31，10： | 2 |
| 4 | Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex Ⅱ via a water molecule mediated binding feature显示文摘The mitochondrial respiratory complex Ⅱ or succinate:ubiquinone oxidoreductase(SQR)is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration.Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography.Crystal structure of the SQR bound with thiabendazole(TBZ)reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role.The obvious inhibitory effect of TBZ based on the biochemical data(IC50~100μmol/L)and the significant structure-based binding affinity calculation(~94μmol/L)draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage. | Qiangjun Zhou Yujia Zhai Jizhong Lou Man Liu Xiaoyun Pang Fei Sun | 2011 | Protein & Cell2011，2，7： | 2 |
| 5 | Ultrashort microwave-induced thermoacoustic imaging: A breakthrough in exei-tation efficiency and spatial resolution显示文摘 | Lou Cunguang Yang Sihua Jizhong | 2012 | Phys Rev Lett2012，109，21： | 1 |
| 6 | CENP-A的Ser68位动态磷酸化调控它在着丝粒区域的细胞周期依赖性装配显示文摘细胞出版社《发育细胞》创刊于2001年,本刊致力于搭建细胞生物学与发育生物学两大学科之间的桥梁。受过专业博士训l练的科学编辑与作者、审稿人、编委会成员共同合作,及时发布横跨两个领域令人振奋的研究成果,强调两个领域之间共同面临的问题以及相互之间的关系。该杂志2015年公布的影响因子为9.708。 | Zhouliang Yu Xiang Zhou Wenjing Wang Wenqiang Deng Junnan Fang Hao Hu Zichen Wang Shangze Li Lei Cui Jing Shen Linhui Zhai Shengyi Peng Jiemin Wong Shuo Dong Zengqiang Yuan Guangshuo Ou Xiaodong Zhang Ping Xu Jizhong Lou Na Yang Ping Chen Rui-Ming Xu 李国红 | 2016 | 科学新闻2016，0，1： | 1 |
| 7 | Mechanochemistry of catch bonds between integrins and ligands显示文摘Integrins are a large family of adhesion molecules broadly expressed on the surface of a wide variety of cells as heterodimers.Binding of integrins to ligands provides anchorage and signals for the cell,making them prime candidates for mechanosensing molecules.To elucidate how force regulates integrin/ligand dissociation,we used molecular mechanics experiments | Fang Kong1,Wei Chen1,Jizhong Lou,Cheng Zhu1-3(1,Woodruff School of Mechanical Engineering,2,Institute for Bioengineering and Bioscience,and 3,Coulter Department of Biomedical Engineering Georgia Institute of Technology,Atlanta,GA 30332-0363cheng) | 2009 | 医用生物力学2009，24，S1： | 0 |
| 8 | Mechanical unfolding of a β-barrel membrane protein by single-molecule force spectroscopy显示文摘Dear Editor.Transmembrane proteins with β-barrel topology are mainly found in the outer membranes(OMs)of Gram-negative bacteria,mitochondria and chloroplasts(Wimley,2003).These proteins usually contain even numbers of β-strands,ranging from 8-36.To achieve an overall cylindrical topology,the polypeptide chain of a β-barrel OMP must fold to form a series of anti-parallel β-strands with each β-strand hydrogen-bonding to its neighboring strands(Otzen and Andersen,2013).The folding and insertion of a β-barrel OMP in vivo requires an evolutionarily conserved multiprotein complex termedβ-barrel assembly machinery(BAM)complex(Noinaj et al.,2015). | Hui Chen Guangtao Song Yong Zhang Dongchun Ni Xinwei Zhang Yihua Huang Jizhong Lou | 2021 | Science China(Life Sciences)2021，64，2： | 0 |
| 9 | 机械力诱导MHC-Ⅰ构象变化增强TCR抗原识别及T细胞活化显示文摘CD8+T细胞主要通过T细胞表面受体(T cell recep tor,TCR)识别并与Ⅰ型主要组织性复合物提呈的抗原(pMHC-Ⅰ)相互作用[1]。TCR对刺激型抗原的识别在CD8+T细胞毒性和适应性免疫中发挥着关键作用。许多证据表明机械力可以延长TCR与刺激性pMHC作用的键合时间(bond lifetime)形成抗原特异性逆锁键(catch bond)[2],并且这种逆锁键对抗原识别非常重要。然而,机械力调控TCR抗原识别的具体结构机制仍不清楚。通过分子动力学模拟、单分子生物膜力学探针、磁镊、T细胞活化实验和动物模型对此问题展开了系统的研究[4]。发现作用在TCR-pMHC-Ⅰ复合体上的拉力可以作用在TCR-pMHC-Ⅰ复合体上的拉力可以打破MHC-I分子内部α1-α2和β2结构域间的相互作用,导致α1-α2结构域旋转并发生构象变化。力诱导的MHC-I构象变化可以进一步别构地调节TCR与刺激性抗原肽及α1-α2结构域的构象及相互作用,诱导产生新的氢键,增强TCR-pMHC-Ⅰ之间的键合时间,但并不能增强TCR与抑制性pMHC-Ⅰ之间的作用。当用点突变阻断这些新形成的氢键,或者α1-α2和β2结构域被二硫键锁住时,最佳力诱导的TCR-pMHC-Ⅰ作用的键合时间明显缩短并且T细胞的活化受到抑制。另外,在人TCR和HLA-A2相互作用中发现了类似机制,并且与肿瘤相关的HLA-A2点突变[3]可以通过限制HLA-A2α1--α2和β2结构域之间的构象打开减弱TCR对肿瘤抗原的识别及T细胞的功能。研究结果表明,机械力诱导的MHC-I构象变化对TCR抗原识别和T细胞活化非常重要,进一步地阐明了机械力调控TCR抗原识别机制,为临床肿瘤的免疫治疗和药物设计提供了新思路和新靶点。 | Peng Wu Tongtong Zhang Baoyu Liu Panyu Fei Lei Cui Rui Qin Huaying Zhu Danmei Yao Ryan Martinez Wei Hu Chenyi An Yong Zhang Junwei Liu Weiwei Yin Jie Sun Chun Zhou Xun Zeng Jianan Wang Brian Evavold Cheng Zhu Jizhong Lou Wei Chen | 2019 | 医用生物力学2019，34，A01： | 0 |
| 10 | Two chemical-controlled switchable Cas9s for tunable gene editing显示文摘INTRODUCTION The clustered regularly interspaced short palindromic repeats (CRISPR) loci and their associated (Casj genes are found in many bacterial and archaeal genomes as adaptive defense systems against phage infection and plasmid transfer (Mohanraju et al. 2016). | Meng Liang Yang Cui Jie Lan Guangtao Song Jizhong Lou | 2019 | Biophysics Reports2019，5，3： | 0 |
| 11 | Measuring the elasticity of liquid–liquid phase separation droplets with biomembrane force probe显示文摘Numerous biomacromolecules undergo liquid–liquid phase separation(LLPS)inside living cells and LLPS plays important roles in their functions.The droplets formed by LLPS molecules are complex fluids and their behavior follows fluid mechanics,thus studies on rheological and material properties are required to gain full insight into the biophysical mechanism of these droplets.Biophysical force spectroscopy techniques are particularly useful in this aspect.Indeed,atomic force microscopy and optical tweezers have been used to quantify the elasticity and the viscoelasticity of LLPS droplets.The Biomembrane Force Probe(BFP)is a single-molecule technique designed to investigate liquid-like objects and is more suitable to quantify the material properties of LLPS droplets,but its usage on LLPS droplets is not yet described.Here we present an experimental protocol to measure the Young’s modulus of LLPS droplets using BFP,we believe that the application of BFP on phase separation studies can be expanded and will be very helpful in deciphering the underlying principles of LLPS. | Min Sun Hui Chen Qinghua Ji Jianhui Xiao Yanzhe Hou Jizhong Lou | 2022 | Biophysics Reports2022，8，2： | 0 |
| 12 | Author Correction: Mechanical activation of spike fosters SARS- CoV-2 infection显示文摘 | Wei Hu Yong Zhang Panyu Fei Tongtong Zhang Danmei Yao Yufei Gao Jia Liu Hui Chen Qiao Lu Tenny Mudianto Xinrui Zhang Chuxuan Xiao Yang Ye Qiming Sun Jing Zhang Qi Xie Pei-Hui Wang Jun Wang Zhenhai Li Jizhong Lou Wei Chen | 2021 | Cell Research2021，31，11： | 0 |
| 13 | The conformational states of talin autoinhibition complex and its activation under forces显示文摘Talin is an integrin-binding protein located at focal adhesion site and serves as both an adapter and a force transmitter. Its integrin binding activity is regulated by the intramolecular autoinhibition interaction between its F3 and RS domains. Here, we used atomic force microscopy to measure the strength of talin autoinhibition complex. Our results suggest that the lifetime of talin autoinhibition complex shows weak catch bond behavior and does not change significantly at smaller forces, while it drops rapidly at larger forces(>10 p N). Moreover, besides the complex conformation revealed by crystal structure, our molecular dynamics(MD) simulations indicate the possible existence of another stable conformation. Further analysis indicates that forces may regulate the equilibrium of the two stable binding states and result in the non-exponential force dependence of the binding lifetime. Our findings reveal a negative regulation mechanism on talin activation and provide a new point of view on the function of talin in focal adhesion. | ZENG Yan ZHANG Yong SONG XianQiang JI QingHua YE Sheng ZHANG RongGuang LOU JiZhong | 2015 | Science China(Life Sciences)2015，58，7： | 0 |
| 14 | Mechanosensing via Immunereceptors显示文摘The immune response is orchestrated by a variety of immune cells,the function of which then is determined by the collective signals from different immunoreceptors.Recent studies have highlighted the presence of mechanical force on these receptor-ligand pairs and its important role in regulating antigen recognition/discrimination and function.In this perspective,we use the T cell receptor as an example to review the current understanding of the mechanosensing properties of immunoreceptors.We discuss the types of forces that immunoreceptors may encounter,the effects on ligand recognition,conformational changes and mechanosensing mechanisms,as well as the consequences in downstream signal transduction and function. | Cheng Zhu Wei Chen Jizhong Lou William Rittase Kaitao Li | 2019 | 医用生物力学2019，34，A01： | 0 |
| 15 | Mechanism of mechanical regulated Notch activation and structural bases of Notch NRR related T-lineage acute lymphoblastic leukemia(T-ALL)显示文摘Notch proteins are transmembrane receptors which can transduce signals between cells.Upon binding to their ligands on the neighboring cells,notch receptors can be activated and undergo conformational changes which enable their proteolysis by ADAM-family of metalloproteases[1].The cleavage site of notch protein located on its hetrodimerizaton domain(HD)of the negative regulatory region(NRR)proximal to the N-terminal of the transmembrane helix.Recent crystal structures on several notch proteins[2-4]indicated that a series of three Lin12/Notch repeats(LNRs)wrap around the HD and bury the cleavage site to prevent it from proteolysis at the normal conditions without ligand binding.Studies indicated that notch/ligand binding may al- | Jizhong Lou | 2013 | 医用生物力学2013，28，S1： | 0 |
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