Article
Multidisciplinary Sciences
Devin T. Edwards, Marc-Andre Leblanc, Thomas T. Perkins
Summary: Single-molecule force spectroscopy was used to study protein folding dynamics, revealing intrinsic changes in protein folding dynamics and transition state height under different pH conditions. Despite differences in destabilization mechanisms, constant-force landscapes showed minimal differences in transition state height, while force-dependent rates increased as pH decreased. This study provides insights for future AFM-based studies of mechanoresponsive proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Polymer Science
Xiaoye Zhang, Dandan Li, Yu Song, Wenke Zhang
Summary: In this study, the mechanical stability and melting pathway of highly stereoregular syndiotactic polypropylene (s-PP) were investigated using atomic force microscopy (AFM)-based single molecule force spectroscopy (SMFS). It was found that crystal thickness and structure have significant impacts on mechanical stability and melting pathway.
Article
Chemistry, Multidisciplinary
Hai Lei, Junsheng Zhang, Ying Li, Xin Wang, Meng Qin, Wei Wang, Yi Cao
Summary: In this study, a histidine-specific phosphorylation strategy was developed to covalently anchor proteins to an atomic force microscopy. This method improved the data quality of single-molecule force spectroscopy experiments and was successfully applied to investigate the mechanical stability and unfolding process of proteins.
Article
Chemistry, Multidisciplinary
Haipei Liu, Zhaowei Liu, Mariana Sa Santos, Michael A. A. Nash
Summary: Single-molecule force spectroscopy (SMFS) is a powerful tool for studying protein folding and mechanical properties. However, the traditional method of immobilization using lysine residues results in a heterogeneous distribution of tether positions. In this study, we compared lysine-based immobilization to site-specific immobilization using genetically encoded peptide tags (ybbR). Our results showed that lysine-based immobilization led to signal deterioration and incorrect classification of unfolding pathways. We also developed a mixed immobilization approach that partially recovered specific signals.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
David R. Jacobson, Thomas T. Perkins
Summary: By using an atomic-force-microscope assay optimized for mechanical force to reversibly unfold local regions of an individual protein, researchers overcame limitations of chemical denaturation assays in understanding the energetics of membrane proteins. This approach provided quantitative insight into the Delta Delta G of single amino acid mutations in membrane proteins and highlighted the contribution of membrane protein-lipid contacts to folding energetics. The platform established allows for determining Delta Delta G for fully folded membrane proteins embedded in their native bilayers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Polymer Science
Song Lu, Wanhao Cai, Song Zhang, Shuxun Cui
Summary: The single-chain mechanics of three kinds of polymers (polydimethylsiloxane, polyoxymethylene, and poly(methyl methacrylate)) were studied from room temperature to 153K using atomic force microscopy-based single-molecule force spectroscopy and a theoretical model. The isolated chain showed a gradual change in its mechanics with temperature, which could be described using an elastic model. Analysis revealed that the single bonds in the backbone of an isolated chain could freely rotate within the timescale of single-molecule manipulation. This study is the first experimental investigation of single-chain mechanics at cryogenic temperatures and supports the theoretical prediction of a much lower transition temperature for isolated chains compared to bulk polymer materials.
Article
Chemistry, Multidisciplinary
Alejandro Valbuena, Klara Strobl, Juan Carlos Gil-Redondo, Luis Valiente, Pedro J. de Pablo, Mauricio G. Mateu
Summary: This study investigates the uncoating process of human rhinovirus particles using an atomic force microscope. The results show that the high-force event is a stochastic process that leads to structurally weakened virus particles, with different fractions of the RNA molecule being externalized. The kinetics of this reaction are influenced by antiviral compounds or capsid mutation.
Article
Polymer Science
Song Lu, Wanhao Cai, Song Zhang, Shuxun Cui
Summary: The single-chain mechanics of three polymers (polydimethylsiloxane, polyoxymethylene, and poly(methyl methacrylate)) were studied at cryogenic temperatures using atomic force microscopy and a theoretical model. The isolated chain exhibited gradual changes in single-chain mechanics, which could be well described by an elastic model. The study also revealed that the single bonds in the backbone of the chain could freely rotate with thermal fluctuations.
Article
Chemistry, Physical
Jingyuan Nie, Yibing Deng, Fang Tian, Shengchao Shi, Peng Zheng
Summary: Cation-pi interaction plays a crucial role in biological systems but its experimental verification and quantification at the molecular level are limited. In this study, atomic force microscopy-based single-molecule force spectroscopy was used to measure the stability and kinetics of NGAL protein with cation-pi interactions. The results demonstrated the high-precision detection of weak cation-pi interaction in NGAL.
Article
Chemistry, Multidisciplinary
Jiacheng Zuo, Hongbin Li
Summary: Scientists have developed an atomic force microscopy (AFM)-based two-molecule force spectroscopy method to directly probe the mechanical properties of parallelly arranged elastomeric proteins. By using a twin-molecule approach, they were able to pick up and stretch two parallelly arranged elastomeric proteins simultaneously in an AFM experiment, revealing the mechanical features and determining the mechanical unfolding forces of proteins in such an experimental setting.
Review
Chemistry, Physical
Mi Li, Lianqing Liu, Tomaso Zambelli
Summary: Fluidic force microscopy (FluidFM), combining AFM with microchanneled cantilevers, allows for force-sensitive nanopipette manipulation under aqueous conditions. It has unique advantages in simultaneous three-dimensional manipulations and mechanical measurements at the micro-/nanoscale, showing great potential in biophysical assays, particularly at the single-cell level.
Article
Chemistry, Physical
Arnab Bera, Mohan Kundu, Bikash Das, Sk Kalimuddin, Satyabrata Bera, Deep Singha Roy, Suman Kalyan Pradhan, Sanjib Naskar, Subodh Kumar De, Biswajit Das, Mintu Mondal
Summary: In this study, electric field-induced conducting states were used in MoTe2 nanoflakes to create nonvolatile resistive memory technologies. The devices showed significant resistive switching characteristics between high and low resistive states, and the conductance fluctuation properties were found to be state-dependent.
APPLIED SURFACE SCIENCE
(2023)
Article
Biology
Andrea Raspadori, Valentina Vignali, Anna Murello, Gabriele Giachin, Bruno Samori, Motomasa Tanaka, Carlos Bustamante, Giampaolo Zuccheri, Giuseppe Legname
Summary: Prion diseases are neurodegenerative disorders characterized by the presence of oligomers and amyloid fibrils. In this study, atomic force microscopy was used to investigate the conformational changes and oligomerization processes of the prion protein. The results showed a complex scenario of structural heterogeneity at the monomeric and dimer levels, and suggested that the C-C dimer orientation may play a role in amyloid fibril formation.
Article
Physics, Multidisciplinary
M. Omidian, S. Leitherer, N. Neel, M. Brandbyge, J. Kroeger
Summary: Through experiments and calculations, we found that under an external electric field, the polar covalent bond between a gold atom and a carbon atom on graphene exhibits different strengths and stabilities depending on the orientation of the field.
PHYSICAL REVIEW LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Marc Mora, Stephanie Board, Olivier Languin-Cattoen, Laura Masino, Guillaume Stirnemann, Sergi Garcia-Manyes
Summary: Non-native disulfide bonds are dynamic covalent bridges formed in proteins, which can be detected using mechanical force and are associated with protein function and aggregation diseases.
Review
Cell Biology
K. Tanuj Sapra, Ohad Medalia
Summary: The eukaryotic cell cytoskeleton is a crucial structural scaffold that supports various biochemical and cellular functions, with the intermediate filament networks playing a key role in providing unique mechanical properties and increasing resilience under mechanical pressure. Mutations in intermediate filaments can lead to architectural integrity and functional issues in cellular processes, highlighting their importance in maintaining cellular function. The remarkable mechanical feature of intermediate filaments lies in their ability to transform under stress, making them one of the strongest and most resilient mechanical entities in nature.
Article
Biochemistry & Molecular Biology
Noah Ritzmann, Selen Manioglu, Sebastian Hiller, Daniel J. Mueller
Summary: The 8-barrel assembly machinery (BAM) complex is important for inserting and folding outer membrane proteins in Escherichia coli. A natural antibiotic compound called darobactin inhibits the central unit, BamA. Using dynamic single-molecule force spectroscopy, researchers were able to study the structure-function relationship of BamA and its inhibition by darobactin.
Article
Cell Biology
Kristyna Pluhackova, Florian M. Wilhelm, Daniel J. Mueller
Summary: Studies have shown that GPCR receptor phosphorylation and local membrane composition cooperatively regulate the conformation and dynamics of the GPCR-arrestin complex, which in turn affects signal transduction and the binding specificity of arrestin. Therefore, a deeper understanding of the complex GPCR regulatory mechanisms is crucial for identifying novel pathways of pharmacological intervention.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Prabhjot Dhami, Lena C. Quilty, Benjamin Schwartzmann, Rudolf Uher, Timothy A. Allen, Stefan Kloiber, Raymond W. Lam, Glenda MacQueen, Benicio N. Frey, Roumen Milev, Daniel J. Mueller, Stephen C. Strother, Pierre Blier, Claudio N. Soares, Sagar V. Parikh, Gustavo Turecki, Jane A. Foster, Susan Rotzinger, Sidney H. Kennedy, Faranak Farzan
Summary: The neurobiological correlates of response inhibition can predict the response of patients with major depressive disorder (MDD) to pharmacological and cognitive behavioral therapy treatment. The integrity of response inhibition may be crucial for the success of treatment for MDD. Electrophysiological correlates of response inhibition may serve as a general prognostic marker for treatment response in MDD.
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
(2023)
Article
Multidisciplinary Sciences
Stefania A. Mari, Kristyna Pluhackova, Joka Pipercevic, Matthew Leipner, Sebastian Hiller, Andreas Engel, Daniel J. Mueller
Summary: Gasdermin-A3 pore formation propagates along diverse pathways, and the assembly and pore-forming mechanisms have been characterized using high-resolution time-lapse atomic force microscopy. The results reveal the role of amphiphilic beta-hairpins and structurally adapting hydrophilic head domains in stabilizing variable oligomeric conformations and opening the pore.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Tetiana Serdiuk, Moutusi Manna, Cheng Zhang, Stefania A. Mari, Waldemar Kulig, Kristyna Pluhackova, Brian K. Kobilka, Ilpo Vattulainen, Daniel J. Muller
Summary: Cholesterol interacts with G protein-coupled receptors in cell membranes, modulating their assembly, stability, and conformation. This study shows that the cholesterol analog CHS can nonlinearly stabilize different structural regions of GPCRs and affect their functionality, with the strongest effects observed at physiological temperature.
Article
Multidisciplinary Sciences
Andreas P. Cuny, K. Tanuj Sapra, David Martinez-Martin, Gotthold Flaschner, Jonathan D. Adams, Sascha Martin, Christoph Gerber, Fabian Rudolf, Daniel J. Mueller
Summary: The regulation of cell growth is of great significance in physiology, biotechnology, and medicine. However, monitoring the mass and growth of individual cells with high resolution is challenging. In this study, the authors modified a cell balance technique to monitor the proliferation of single yeast cells in real-time. They found that the mass of single yeast cells increases in linear segments of constant growth rates. This technology has the potential to directly and accurately monitor the growth of single cells throughout their cycle.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Selen Manioglu, Seyed Majed Modaresi, Noah Ritzmann, Johannes Thoma, Sarah A. Overall, Alexander Harms, Gregory Upert, Anatol Luther, Alexander B. Barnes, Daniel Obrecht, Daniel J. Muller, Sebastian Hiller
Summary: The study uses high-resolution atomic force microscopy to investigate the interaction mechanism between Polymyxins and bacterial membranes. The results show that Polymyxins can arrange bacterial lipids into regular hexagonal structures, making the membrane stiffer and leading to rupture.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Ilaria Incaviglia, Sophie Herzog, Gotthold Flaeschner, Nico Strohmeyer, Enrico Tosoratti, Daniel J. Mueller
Summary: Researchers design photothermally actuated microcantilevers to optimize the accuracy of cell mass measurements. By reducing the inertial mass of the microcantilever using a focused ion beam, they considerably increase its mass sensitivity. The improved microcantilevers allow for more accurate monitoring of cell mass and restrict cell migration, reducing measurement errors.
Article
Biochemistry & Molecular Biology
Nina Blaimschein, Parameswaran Hariharan, Selen Manioglu, Lan Guan, Daniel J. Muller
Summary: In this study, single-molecule force spectroscopy was used to investigate the substrate-induced structural changes of MelB from Salmonella typhimurium. The results showed that in the absence of substrate, MelB equally populated two different states, with one state showing higher mechanical structural stability. However, in the presence of melibiose or a coupling Na+-cation, MelB increasingly populated a mechanically less stable state. In the presence of both substrate and co-substrate, this mechanically less stable state of MelB was predominant. These findings provide mechanistic insights into the symport action of galactosides and cations catalyzed by MelB.
Article
Biochemistry & Molecular Biology
Hella Baumann, Melanie Schwingel, Marcello Sestu, Anna Burcza, Susanna Marg, Wolfgang Ziegler, Anna V. V. Taubenberger, Daniel J. J. Muller, Martin Bastmeyer, Clemens M. M. Franz
Summary: This study investigated the role of vinculin in the reinforcement of nascent adhesions between cells and fibronectin or vitronectin. The researchers found that vinculin is dispensable for adhesion initiation but is crucial for adhesion strength and traction after 60 to 120 seconds. Re-expression of full-length vinculin or a constitutively active vinculin mutant restored adhesion and traction, while vinculin with specific mutations was ineffective.
JOURNAL OF MOLECULAR RECOGNITION
(2023)
Article
Multidisciplinary Sciences
Morris Degen, Jose Carlos Santos, Kristyna Pluhackova, Gonzalo Cebrero, Saray Ramos, Gytis Jankevicius, Ella Hartenian, Undina Guillerm, Stefania A. Mari, Bastian Kohl, Daniel J. Mueller, Paul Schanda, Timm Maier, Camilo Perez, Christian Sieben, Petr Broz, Sebastian Hiller
Summary: Eukaryotic cells can undergo different forms of programmed cell death, many of which culminate in plasma membrane rupture. The protein ninjurin-1 (NINJ1) mediates the active process of membrane rupture in dying cells. NINJ1 clusters into structurally diverse assemblies in dying cell membranes, particularly large filamentous assemblies with branched morphology. Molecular dynamics simulations show that NINJ1 can stably cap membrane edges. Therefore, NINJ1 is an interactive component of the eukaryotic cell membrane that functions as an in-built breaking point in response to activation of cell death.
Article
Multidisciplinary Sciences
Maximilian Huber, Javier Casares-Arias, Reinhard Faessler, Daniel J. Mueller, Nico Strohmeyer
Summary: Adopting a round cell morphology before mitosis is crucial. The authors found that, unlike interphase cells, mitotic cells cannot reinforce cell-ECM adhesion by engaging newly bound integrins via talin or vinculin. However, beta 1 integrins strengthen cell-cell adhesion in mitosis. This dual role of integrins weakens cell-ECM adhesion and strengthens cell-cell adhesion to prevent cell delamination during rounding and dividing.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Anna Stier, Samuel Gilberto, Weaam Mohamed, Lars N. Royall, Jonne Helenius, Ivan Mikicic, Tatjana Sajic, Petra Beli, Daniel J. Mueller, Sebastian Jessberger, Matthias Peter
Summary: CUL4A and CUL4B are paralogs that assemble cullin-RING E3 ubiquitin ligase (CRL) complexes regulating chromatin-associated cellular functions. The unique N-terminal extension of CUL4B is heavily phosphorylated during mitosis, and this phosphorylation is disrupted in the CUL4B-P50L mutation causing X-linked intellectual disability (XLID). Phenotypic characterization and mutational analysis showed that CUL4B phosphorylation is essential for mitosis progression and controls spindle positioning and cortical tension.
Article
Chemistry, Multidisciplinary
Seungkuk Ahn, Upnishad Sharma, Krishna Chaitanya Kasuba, Nico Strohmeyer, Daniel J. J. Muller
Summary: This study introduces a simple and scalable method to engineer biomimetic 3D fibrillar fibronectin matrices and characterizes how fibroblasts sense and adhere to these matrices. The findings demonstrate that fibroblasts accelerate adhesion initiation and strengthening to fibrillar fibronectin matrices compared to globular fibronectin. This immediate sensing and adhesion to fibrillar fibronectin also guide migration speed, persistency, and proliferation range in fibroblasts.
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)
