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
Multidisciplinary Sciences
Takanori Harashima, Shintaro Fujii, Yuki Jono, Tsuyoshi Terakawa, Noriyuki Kurita, Satoshi Kaneko, Manabu Kiguchi, Tomoaki Nishino
Summary: The electrical properties of DNA in the field of molecular electronics have been extensively studied, with a focus on the higher-order structures and design changes associated with single-molecule electronic devices. Researchers have developed a DNA zipper configuration to form a single-molecule junction, which exhibits high conductivity and an attractive self-restoring capability. This strategy provides a basis for novel designs of single-molecule junctions.
NATURE COMMUNICATIONS
(2021)
Review
Nanoscience & Nanotechnology
Hongliang Chen, Chuancheng Jia, Xin Zhu, Chen Yang, Xuefeng Guo, J. Fraser Stoddart
Summary: Developing new materials is a long-standing goal in various fields, and understanding single-molecule reactions can deepen our understanding of chemical reactions and provide new frameworks in materials science. This review focuses on state-of-the-art chemical reactions in single-molecule junctions and highlights the advantages of real-time testbeds for studying reaction dynamics, intermediates, transition states, and solvent effects. The behavior of single-molecule reactions is compared with reactions in ensemble states, and the potential of leveraging single-molecule catalysis for large-scale materials production is explored.
NATURE REVIEWS MATERIALS
(2023)
Article
Multidisciplinary Sciences
Linfei Li, Jeremy F. Schultz, Sayantan Mahapatra, Zhongyi Lu, Xu Zhang, Nan Jiang
Summary: By using ultrahigh vacuum tip-enhanced Raman spectroscopy (UHV-TERS), single oxygen adatoms on a boron monolayer (borophene) can be identified and mapped with a spatial resolution of approximately 4.8 angstrom and single bond sensitivity. This technique enables the atomically defined, chemically homogeneous, and thermally reversible oxidation of borophene via atomic oxygen in UHV. Additionally, it reveals the propensity of borophene towards molecular oxygen activation at room temperature and phase-dependent chemical properties. Overall, this work demonstrates the powerful utility of UHV-TERS in probing the local chemistry of surface adsorbates in the atomic regime and has important applications in heterogeneous catalysis, on-surface molecular engineering, and low-dimensional materials.
NATURE COMMUNICATIONS
(2022)
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
Biochemical Research Methods
Chen Yang, Caiyao Yang, Yilin Guo, Jianfei Feng, Xuefeng Guo
Summary: The ability to measure the behavior of a single molecule during a reaction can uncover dynamic and static disordered states that may not be represented in ensemble averages. This article introduces a method to build devices with graphene-molecule-graphene single-molecule junctions integrated into an electrical circuit. These devices are stable, tolerant to mechanical changes and solution environments, and enable sensitive detection of variations in physical and chemical properties of detected molecules. The on-chip setup of single-molecule junctions also allows for logic functions and analysis of reaction intermediates.
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.
Review
Biochemistry & Molecular Biology
Rebeca Bocanegra, Ismael G. A. Plaza, Carlos R. Pulido, Borja Ibarra
Summary: The study reveals that the replisome machinery is stochastic, versatile, and highly dynamic, with transient protein-protein and protein-DNA interactions playing a key role in robust DNA replication.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
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
Polymer Science
Lu Qian, Kai Zhang, Xin Guo, Junyu Zhou, Miao Yu
Summary: The study found that there was almost no difference in the single-chain elasticity of gelatin in nonane and DI water. When a single gelatin chain is pulled into loose nonane, dehydration does not occur due to strong binding water interactions. Gelatin chains can only interact with water molecules at high temperatures.
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
Biochemistry & Molecular Biology
Manish Bajaj, Mohd Muddassir, Bumjoon Choi, Priyanka Singh, Jong Bum Park, Surjeet Singh, Manisha Yadav, Rajesh Kumar, Kilho Eom, Deepak Sharma
Summary: This study investigates the effect of osmolytes on the mechanical unfolding properties of protein domain using atomic force microscopy. The results show that amines and methylamines enhance the mechanical stability of the protein, while polyols have no effect. Glycine betaine and trimethylamine-N-oxide increase the average unfolding force of the protein domain. These findings have potential applications in modulating the mechanical stability of proteins for nano-biotechnological purposes.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Biochemistry & Molecular Biology
Rafayel Petrosyan, Abhishek Narayan, Michael T. Woodside
Summary: Single-molecule force spectroscopy (SMFS) is a powerful tool for studying protein folding dynamics, uncovering energy landscapes of folding, complex folding pathways, mechanisms of chaperones in assisting folding, effects of ribosomes on co-translational folding, and monitoring membrane protein folding.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Physics, Applied
Shuai Li, Haiqing Liu, Chunguang Hu, Chengzhi He, Huizhu Hu
Summary: This study investigated the mechanical unfolding of protein domains in monomeric protein NuG2 and tandem polyproteins. By stretching these proteins, the mechanical unfolding force of each domain and energy dissipation were determined, paving the way for engineering artificial polyproteins with controllable force and energy properties.
APPLIED PHYSICS EXPRESS
(2022)
Article
Chemistry, Multidisciplinary
Marta Urbanska, Annemarie Ludecke, Wilhelm J. Walter, Antoine M. van Oijen, Karl E. Duderstadt, Stefan Diez
Summary: This study introduces a highly-parallel, microfluidics-based method for rapid collection of force-dependent motility parameters of cytoskeletal motors, significantly improving throughput. DNA-tethered beads are used to apply tunable hydrodynamic forces to stepping kinesin-1 motors, allowing for simultaneous tracking of various motility parameters of hundreds of individual molecules. The approach, applicable to other molecular systems, represents a new methodology for parallelized single-molecule force studies on cytoskeletal motors.
Article
Multidisciplinary Sciences
Hsuan Lee, Chih-Chieh Yu, Edward S. Boyden, Xiaowei Zhuang, Pallav Kosuri
Summary: The accuracy of gel embedding in expansion microscopy was quantified using STORM, revealing random displacements of labeled sites with polyacrylamide hydrogels but preserved positions with tetra-gel. Combining tetra-gel ExM with STORM enabled resolution of 11-nm structural features without loss in accuracy, offering a way to improve super-resolution microscopy.
SCIENTIFIC REPORTS
(2021)
Article
Materials Science, Biomaterials
Marina Slawinski, Luai R. Khoury, Sabita Sharma, Joel Nowitzke, Jennifer H. Gutzman, Ionel Popa
Summary: Hydrogels made from covalently cross-linked globular proteins are emerging as important biomaterials with various applications. They offer a promising system to study protein unfolding in crowded environments, and our method introduces micrometer-sized pores and increased permeability to these protein materials without sacrificing their mechanical characteristics.
ACS BIOMATERIALS SCIENCE & ENGINEERING
(2022)
Review
Biochemistry & Molecular Biology
Carmen Suay-Corredera, Jorge Alegre-Cebollada
Summary: Hypertrophic cardiomyopathy (HCM) is the most common inherited disorder of the heart, characterized by cardiac muscle hypertrophy and hypercontractility. This review summarizes the clinical and genetic aspects of HCM and provides updated information on therapeutic options targeting sarcomere mechanical activity. The authors also discuss the correlation between altered mechanical properties of cMyBP-C and HCM development.
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.
Article
Biochemistry & Molecular Biology
Elias Herrero-Galan, Ines Martinez-Martin, Cristina Sanchez-Gonzalez, Natalia Vicente, Elena Bonzon-Kulichenko, Enrique Calvo, Carmen Suay-Corredera, Maria Rosaria Pricolo, Angel Fernandez-Trasancos, Diana Velazquez-Carreras, Claudio Badia Careaga, Mahmoud Abdellatif, Simon Sedej, Peter P. Rainer, David Giganti, Raul Perez-Jimenez, Jesus Vazquez, Jorge Alegre-Cebollada
Summary: Titin's mechanical properties can be modulated by oxidative modifications of cysteines, which may contribute to the pathogenesis of heart disease.
Article
Chemistry, Multidisciplinary
Ionel Popa, Florin Saitis
Summary: This study reports on a novel approach to teach protein folding and unfolding using magnets and flexible 3D-printed protein structures. The experiments demonstrated the unfolding of proteins under force, providing a new way to understand protein folding and mechanical unfolding.
JOURNAL OF CHEMICAL EDUCATION
(2022)
Article
Chemistry, Physical
Joel Nowitzke, Ionel Popa
Summary: This research introduces a new method to estimate the average force-per-molecule for materials made from globular proteins and successfully synthesizes protein hydrogels. The study shows that concentration is the most sensitive parameter affecting molecular forces.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Multidisciplinary Sciences
Narayan Dahal, Sabita Sharma, Binh Phan, Annie Eis, Ionel Popa
Summary: The study found that the R8 domain of talin displays memory-dependent behavior under force, indicating the evolution of a unique force-induced native state. It was also discovered that talin R8 domain binds its ligand DLC1 with much higher affinity than previously reported. This interaction may explain the anti-tumor response of DLC1 by regulating the inside-out activation of integrins.
Article
Engineering, Biomedical
Ion Andreu, Ignasi Granero-Moya, Sergi Garcia-Manyes, Pere Roca-Cusachs
Summary: Cell nuclei are affected by mechanical forces, especially through the mechanical regulation of nucleocytoplasmic transport mediated by nuclear pore complexes. Mechanical forces can increase the permeability of nuclear pore complexes by exerting force on the nucleus, and the mechanical properties of transported proteins can also regulate the rate of nucleocytoplasmic transport.
APL BIOENGINEERING
(2022)
Review
Nanoscience & Nanotechnology
Amy E. M. Beedle, Sergi Garcia-Manyes
Summary: This review discusses single-molecule force spectroscopy experiments conducted on proteins involved in mechanosensing and mechanotransduction in eukaryotic cells. Mechanical forces are emerging as a major regulator of human physiology. Single-molecule nanomechanical techniques have allowed us to gain comprehensive knowledge of the physicochemical principles governing the elasticity of single proteins and its role in mechanosensing and mechanotransduction.
NATURE REVIEWS MATERIALS
(2023)
Article
Engineering, Biomedical
Angela Perez-Benito, Carla Huerta-Lopez, Jorge Alegre-Cebollada, Jose Manuel Garcia-Aznar, Silvia Hervas-Raluy
Summary: Protein-based hydrogels are extensively studied in biomaterials research due to their ability to mimic living tissues and the extracellular matrix. However, methods for controlling their mechanical properties are limited, mainly focusing on elasticity and often with unrealistic characterization. This study develops a computational model to characterize the mechanical behavior of two protein-based hydrogels and compares it with experimental results. The model utilizes the Finite Element Method, combining hyperelastic and viscoelastic models, and the first order Ogden model with a viscoelastic model defined in Prony parameters performs the best in reproducing the observed strain-stress response and stiffness change.
JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
(2023)
Article
Physics, Multidisciplinary
Rafael Tapia-Rojo, Marc Mora, Stephanie Board, Jane Walker, Rajaa Boujemaa-Paterski, Ohad Medalia, Sergi Garcia-Manyes
Summary: By using single-molecule magnetic tweezers, researchers have observed previously inaccessible rare conformations of the talin protein and investigated its folding dynamics over extended periods of time. This study sheds light on the complex landscapes of protein folding and highlights the importance of observation timescale in understanding equilibrium dynamics.
Article
Multidisciplinary Sciences
Florian Franz, Rafael Tapia-Rojo, Sabina Winograd-Katz, Rajaa Boujemaa-Paterski, Wenhong Li, Tamar Unger, Shira Albeck, Camilo Aponte-Santamaria, Sergi Garcia-Manyes, Ohad Medalia, Benjamin Geiger, Frauke Graeter
Summary: This study reveals that talin activates vinculin through an intricate allosteric mechanism regulated by force. The interaction between vinculin and talin plays a crucial role in mechanosensing in cells.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Einat Chetrit, Sabita Sharma, Uri Maayan, Maya Georgia Pelah, Ziv Klausner, Ionel Popa, Ronen Berkovich
Summary: Polyproteins play important roles in cellular mechanisms, but their unfolding kinetics can exhibit nonexponential behavior under different force loads.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2022)
Meeting Abstract
Biophysics
Narayan Dahal, Sabita Sharma, Binh Phan, Annie Eis, Ionel Popa
BIOPHYSICAL JOURNAL
(2022)
