scholarly journals Interaction of theory and experiment: examples from single molecule studies of nanoparticles

2010 ◽  
Vol 368 (1914) ◽  
pp. 1109-1124 ◽  
Author(s):  
Rudolph A. Marcus
Keyword(s):  
Single Molecule ◽  
Large Body ◽  
Surface States ◽  
Biological Species ◽  
Theoretical Chemistry ◽  
Past Half Century ◽  
Single Molecule Studies ◽  
Computer Calculations ◽  
Complementary Nature

This article is in part the author's perspective on the revolution that has occurred in theoretical chemistry during the past half-century. In this period much of theoretical chemistry has moved from its initial emphasis on analytic treatments, resulting in equations for physical chemical and chemical phenomena, to the detailed computation of many different systems and processes. In the best sense the old and the new are complementary and their coexistence can benefit both. Experiment too has seen major developments. One of the newer types of experiment is that of single molecule studies. They range from those on small inorganic and organic nanoparticles to large biological species. We illustrate some of the issues that arise, using the topic of ‘quantum dots’ (QDs), and choosing a particular inorganic nanoparticle, CdSe, the most studied of these systems. Its study reflects the problems that arise in experiment and in theories in this field. The complementary nature of the conventional ensemble experiments and the new single molecule experiments is described and is illustrated by trajectories for the two types of experiments. The research in the QD field is both experimentally and theoretically a currently ongoing process, for which the answers are not fully known in spite of the large body of research. The detailed role of surface states is part of the problem. The field continues to yield new and unexpected results. In a sense this part of the article is an interim report that illustrates one analytic approach to the topic and where computer calculations and simulations can be expected to provide added insight.

scholarly journals Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER

2021 ◽  
Vol 7 (21) ◽  
pp. eabg0942
Author(s):  
Jae Ho Lee ◽  
Ahmad Jomaa ◽  
SangYoon Chung ◽  
Yu-Hsien Hwang Fu ◽  
Ruilin Qian ◽  
...  
Keyword(s):  
Single Molecule ◽  
Protein Translocation ◽  
Molecular Model ◽  
Genetic Diseases ◽  
Signal Recognition Particle ◽  
Biological Regulation ◽  
Single Molecule Studies ◽  
Guanosine Triphosphatase ◽  
Gtpase Cycle

The conserved signal recognition particle (SRP) cotranslationally delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum (ER). The molecular mechanism by which eukaryotic SRP transitions from cargo recognition in the cytosol to protein translocation at the ER is not understood. Here, structural, biochemical, and single-molecule studies show that this transition requires multiple sequential conformational rearrangements in the targeting complex initiated by guanosine triphosphatase (GTPase)–driven compaction of the SRP receptor (SR). Disruption of these rearrangements, particularly in mutant SRP54G226E linked to severe congenital neutropenia, uncouples the SRP/SR GTPase cycle from protein translocation. Structures of targeting intermediates reveal the molecular basis of early SRP-SR recognition and emphasize the role of eukaryote-specific elements in regulating targeting. Our results provide a molecular model for the structural and functional transitions of SRP throughout the targeting cycle and show that these transitions provide important points for biological regulation that can be perturbed in genetic diseases.

scholarly journals Real time observation of chaperone-modulated talin mechanics under single molecule resolution

2021 ◽  
Author(s):  
Souradeep Banerjee ◽  
Deep Chaudhuri ◽  
Soham Chakraborty ◽  
Shubhasis Haldar
Keyword(s):  
Focal Adhesion ◽  
Single Molecule ◽  
Mechanical Stability ◽  
Energy Landscape ◽  
Magnetic Tweezers ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Single Molecule Studies ◽  
Time Observation

AbstractRecent single molecule studies have recognized talin as a mechanosensitive hub in focal adhesion, where its function is strongly regulated by mechanical force. For instance, at low force (less than 5pN), folded talin binds RIAM for integrin activation; whereas at high force (more than 5pN), it unfolds to activate vinculin binding for focal adhesion stabilization. Being a cytoplasmic large protein, talin must interact with various chaperones, however the role of chaperones on talin mechanics is unknown.To address this question, we investigated the force response of a mechanically stable talin domain, with a set of well-known holdase and foldase chaperones, using a single molecule magnetic tweezers technology. Our findings demonstrate a novel mechanical role of chaperones. We found holdase chaperones reduce the mechanical stability of the protein to ~6 pN, while the foldase chaperone increases it up to ~15 pN. The alteration in mechanical stability ascribes to the underlying molecular mechanism where the chaperones directly reshape the energy landscape of talin. For example, unfoldase chaperone (DnaK) decreases the unfolding barrier height from 26.8 to 21.69 kBT and increases the refolding barrier from 3.49 to 11.31 kBT. In contrast, foldase chaperone (DsbA) increases the unfolding barrier to 33.46 kBT and decreases the refolding barrier to 0.44 kBT. The quantitative mapping of the chaperone-induced free energy landscape of talin directly shows that chaperones could perturb the focal adhesion dynamics, which in turn can influence downstream signaling cascades in diverse cellular processes.

The localized electron: magnetic properties

2018 ◽  
Author(s):  
Jean-Pierre Launay ◽  
Michel Verdaguer
Keyword(s):  
Single Molecule ◽  
Model Systems ◽  
Ferromagnetic Coupling ◽  
Single Chain ◽  
Single Molecule Magnets ◽  
Magnetic Systems ◽  
Orbital Interactions ◽  
Prussian Blue Analogues ◽  
Mononuclear Complexes

After preliminaries about electron properties, and definitions in magnetism, one treats the magnetism of mononuclear complexes, in particular spin cross-over, showing the role of cooperativity and the sensitivity to external perturbations. Orbital interactions and exchange interaction are explained in binuclear model systems, using orbital overlap and orthogonality concepts to explain antiferromagnetic or ferromagnetic coupling. The phenomenologically useful Spin Hamiltonian is defined. The concepts are then applied to extended molecular magnetic systems, leading to molecular magnetic materials of various dimensionalities exhibiting bulk ferro- or ferrimagnetism. An illustration is provided by Prussian Blue analogues. Magnetic anisotropy is introduced. It is shown that in some cases, a slow relaxation of magnetization arises and gives rise to appealing single-ion magnets, single-molecule magnets or single-chain magnets, a route to store information at the molecular level.

scholarly journals The MAL Protein, an Integral Component of Specialized Membranes, in Normal Cells and Cancer

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1065
Author(s):  
Armando Rubio-Ramos ◽  
Leticia Labat-de-Hoz ◽  
Isabel Correas ◽  
Miguel A. Alonso
Keyword(s):  
Epithelial Cells ◽  
Large Body ◽  
Original Description ◽  
Cell Types ◽  
Future Research ◽  
Transmembrane Segments ◽  
Epsilon Toxin ◽  
Proteolipid Proteins ◽  
Polarized Epithelial Cells

The MAL gene encodes a 17-kDa protein containing four putative transmembrane segments whose expression is restricted to human T cells, polarized epithelial cells and myelin-forming cells. The MAL protein has two unusual biochemical features. First, it has lipid-like properties that qualify it as a member of the group of proteolipid proteins. Second, it partitions selectively into detergent-insoluble membranes, which are known to be enriched in condensed cell membranes, consistent with MAL being distributed in highly ordered membranes in the cell. Since its original description more than thirty years ago, a large body of evidence has accumulated supporting a role of MAL in specialized membranes in all the cell types in which it is expressed. Here, we review the structure, expression and biochemical characteristics of MAL, and discuss the association of MAL with raft membranes and the function of MAL in polarized epithelial cells, T lymphocytes, and myelin-forming cells. The evidence that MAL is a putative receptor of the epsilon toxin of Clostridium perfringens, the expression of MAL in lymphomas, the hypermethylation of the MAL gene and subsequent loss of MAL expression in carcinomas are also presented. We propose a model of MAL as the organizer of specialized condensed membranes to make them functional, discuss the role of MAL as a tumor suppressor in carcinomas, consider its potential use as a cancer biomarker, and summarize the directions for future research.

scholarly journals Hopping and Flipping of RNA Polymerase on DNA during Recycling for Reinitiation after Intrinsic Termination in Bacterial Transcription

2021 ◽  
Vol 22 (5) ◽  
pp. 2398
Author(s):  
Wooyoung Kang ◽  
Seungha Hwang ◽  
Jin Young Kang ◽  
Changwon Kang ◽  
Sungchul Hohng
Keyword(s):  
Single Molecule ◽  
Transcription Initiation ◽  
Molecular Mechanisms ◽  
Facilitated Diffusion ◽  
One Dimensional ◽  
Bacterial Transcription ◽  
Fluorescence Measurements ◽  
Dimensional Diffusion ◽  
Single Molecule Studies ◽  
Hopping Diffusion

Two different molecular mechanisms, sliding and hopping, are employed by DNA-binding proteins for their one-dimensional facilitated diffusion on nonspecific DNA regions until reaching their specific target sequences. While it has been controversial whether RNA polymerases (RNAPs) use one-dimensional diffusion in targeting their promoters for transcription initiation, two recent single-molecule studies discovered that post-terminational RNAPs use one-dimensional diffusion for their reinitiation on the same DNA molecules. Escherichia coli RNAP, after synthesizing and releasing product RNA at intrinsic termination, mostly remains bound on DNA and diffuses in both forward and backward directions for recycling, which facilitates reinitiation on nearby promoters. However, it has remained unsolved which mechanism of one-dimensional diffusion is employed by recycling RNAP between termination and reinitiation. Single-molecule fluorescence measurements in this study reveal that post-terminational RNAPs undergo hopping diffusion during recycling on DNA, as their one-dimensional diffusion coefficients increase with rising salt concentrations. We additionally find that reinitiation can occur on promoters positioned in sense and antisense orientations with comparable efficiencies, so reinitiation efficiency depends primarily on distance rather than direction of recycling diffusion. This additional finding confirms that orientation change or flipping of RNAP with respect to DNA efficiently occurs as expected from hopping diffusion.

scholarly journals Role of Long Non-Coding RNAs and the Molecular Mechanisms Involved in Insulin Resistance

2021 ◽  
Vol 22 (14) ◽  
pp. 7256
Author(s):  
Vianet Argelia Tello-Flores ◽  
Fredy Omar Beltrán-Anaya ◽  
Marco Antonio Ramírez-Vargas ◽  
Brenda Ely Esteban-Casales ◽  
Napoleón Navarro-Tito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Biological Species ◽  
Necrosis Factor Alpha ◽  
Polypyrimidine Tract Binding Protein ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs) are single-stranded RNA biomolecules with a length of >200 nt, and they are currently considered to be master regulators of many pathological processes. Recent publications have shown that lncRNAs play important roles in the pathogenesis and progression of insulin resistance (IR) and glucose homeostasis by regulating inflammatory and lipogenic processes. lncRNAs regulate gene expression by binding to other non-coding RNAs, mRNAs, proteins, and DNA. In recent years, several mechanisms have been reported to explain the key roles of lncRNAs in the development of IR, including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), imprinted maternal-ly expressed transcript (H19), maternally expressed gene 3 (MEG3), myocardial infarction-associated transcript (MIAT), and steroid receptor RNA activator (SRA), HOX transcript antisense RNA (HOTAIR), and downregulated Expression-Related Hexose/Glucose Transport Enhancer (DREH). LncRNAs participate in the regulation of lipid and carbohydrate metabolism, the inflammatory process, and oxidative stress through different pathways, such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), polypyrimidine tract-binding protein 1/element-binding transcription factor 1c (PTBP1/SREBP-1c), AKT/nitric oxide synthase (eNOS), AKT/forkhead box O1 (FoxO1), and tumor necrosis factor-alpha (TNF-α)/c-Jun-N-terminal kinases (JNK). On the other hand, the mechanisms linked to the molecular, cellular, and biochemical actions of lncRNAs vary according to the tissue, biological species, and the severity of IR. Therefore, it is essential to elucidate the role of lncRNAs in the insulin signaling pathway and glucose and lipid metabolism. This review analyzes the function and molecular mechanisms of lncRNAs involved in the development of IR.

Breaking Down the Supramolecular Ensemble: Single-Molecule Studies of the Concentration Dependence of Main-Chain Supramolecular Polymer Molecular Weight Distributions on Surfaces

2010 ◽  
Vol 63 (4) ◽  
pp. 624
Author(s):  
Michael J. Serpe ◽  
Jason R. Whitehead ◽  
Stephen L. Craig
Keyword(s):  
Molecular Weight ◽  
Single Molecule ◽  
Monomer Concentration ◽  
Supramolecular Polymer ◽  
Force Microscopy ◽  
Molecular Weight Distributions ◽  
Atomic Force ◽  
Multi Stage ◽  
Single Molecule Studies ◽  
Supramolecular Ensemble

Single molecule atomic force microscopy (AFM) studies of oligonucleotide-based supramolecular polymers on surfaces are used to examine the molecular weight distribution of the polymers formed between a functionalized surface and an AFM tip as a function of monomer concentration. For the concentrations examined here, excellent agreement with a multi-stage open association model of polymerization is obtained, without the need to invoke additional contributions from secondary steric interactions at the surface.

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