scholarly journals The engineered peptide construct NCAM1-Aβ inhibits aggregation of the human prion protein (PrP)

2021 ◽  
Author(s):  
Maciej Gielnik ◽  
Lilia Zhukova ◽  
Igor Zhukov ◽  
Astrid Gräslund ◽  
Maciej Kozak ◽  
...  
Keyword(s):  
Prion Protein ◽  
Molecular Mechanisms ◽  
Prion Diseases ◽  
Disease Treatment ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Imaging ◽  
Human Prion Protein ◽  
Infected Cells ◽  
Treatment Procedures

AbstractIn prion diseases, the prion protein (PrP) becomes misfolded and forms fibrillar aggregates, which are resistant to proteinase degradation and become responsible for prion infectivity and pathology. So far, no drug or treatment procedures have been approved for prion disease treatment. We have previously shown that engineered cell-penetrating peptide constructs can reduce the amount of prion aggregates in infected cells. The molecular mechanisms underlying this effect are however unknown. Here, we use atomic force microscopy (AFM) imaging to show that the aggregation of the human PrP protein can be inhibited by equimolar amounts of the 25 residues long engineered peptide construct NCAM1-Aβ.

Brittle Behaviour in Aspirin Crystals: Evidence of Spalling Fracture

2020 ◽  
Author(s):  
Benjamin P. A. Gabriele ◽  
Craig J. Williams ◽  
Douglas Stauffer ◽  
Brian Derby ◽  
Aurora J. Cruz-Cabeza
Keyword(s):  
Surface Roughness ◽  
Atomic Force Microscopy ◽  
Single Crystals ◽  
Spalling Fracture ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Imaging

<div> <div> <div> <p>Single crystals of aspirin form I were cleaved and indented on their dominant face. Upon inspection, it was possible to observe strongly anisotropic shallow lateral cracks due to the extreme low surface roughness after cleavage. Atomic Force Microscopy (AFM) imaging showed spalling fractures nucleating from the indent corners, forming terraces with a height of one or two interplanar spacings d100. The formation of such spalling fractures in aspirin was rationalised using basic calculations of attachment energies, showing how (100) layers are poorly bonded when compared to their relatively higher intralayer bonding. An attempt at explaining the preferential propagation of these fractures along the [010] direction is discussed. </p> </div> </div> </div>

Brittle Behaviour in Aspirin Crystals: Evidence of Spalling Fracture

2020 ◽  
Author(s):  
Benjamin P. A. Gabriele ◽  
Craig J. Williams ◽  
Douglas Stauffer ◽  
Brian Derby ◽  
Aurora J. Cruz-Cabeza
Keyword(s):  
Surface Roughness ◽  
Atomic Force Microscopy ◽  
Single Crystals ◽  
Spalling Fracture ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Imaging

<div> <div> <div> <p>Single crystals of aspirin form I were cleaved and indented on their dominant face. Upon inspection, it was possible to observe strongly anisotropic shallow lateral cracks due to the extreme low surface roughness after cleavage. Atomic Force Microscopy (AFM) imaging showed spalling fractures nucleating from the indent corners, forming terraces with a height of one or two interplanar spacings d100. The formation of such spalling fractures in aspirin was rationalised using basic calculations of attachment energies, showing how (100) layers are poorly bonded when compared to their relatively higher intralayer bonding. An attempt at explaining the preferential propagation of these fractures along the [010] direction is discussed. </p> </div> </div> </div>

scholarly journals Atomic force microscopy analysis of native infectious and inactivated SARS-CoV-2 virions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sébastien Lyonnais ◽  
Mathilde Hénaut ◽  
Aymeric Neyret ◽  
Peggy Merida ◽  
Chantal Cazevieille ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Native Conformation ◽  
Force Microscopy ◽  
Enveloped Virus ◽  
Atomic Force ◽  
Afm Imaging ◽  
Level 3 ◽  
Microscopy Analysis ◽  
Virus Morphology ◽  
Nanoscale Level

AbstractSARS-CoV-2 is an enveloped virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. Here, single viruses were analyzed by atomic force microscopy (AFM) operating directly in a level 3 biosafety (BSL3) facility, which appeared as a fast and powerful method to assess at the nanoscale level and in 3D infectious virus morphology in its native conformation, or upon inactivation treatments. AFM imaging reveals structurally intact infectious and inactivated SARS-CoV-2 upon low concentration of formaldehyde treatment. This protocol combining AFM and plaque assays allows the preparation of intact inactivated SARS-CoV-2 particles for safe use of samples out of level 3 laboratory to accelerate researches against the COVID-19 pandemic. Overall, we illustrate how adapted BSL3-AFM is a remarkable toolbox for rapid and direct virus analysis based on nanoscale morphology.

scholarly journals Backbone NMR assignments of the C-terminal domain of the human prion protein and its disease‐associated T183A variant

2021 ◽  
Vol 15 (1) ◽  
pp. 193-196
Author(s):  
Máximo Sanz-Hernández ◽  
Alfonso De Simone
Keyword(s):  
Prion Protein ◽  
Nmr Assignments ◽  
Chemical Shifts ◽  
Prion Diseases ◽  
Random Coil ◽  
Transmissible Spongiform Encephalopathies ◽  
Globular Domain ◽  
Structural Elements ◽  
Spongiform Encephalopathies ◽  
Human Prion Protein

AbstractTransmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders associated with the misfolding and aggregation of the human prion protein (huPrP). Despite efforts into investigating the process of huPrP aggregation, the mechanisms triggering its misfolding remain elusive. A number of TSE-associated mutations of huPrP have been identified, but their role at the onset and progression of prion diseases is unclear. Here we report the NMR assignments of the C-terminal globular domain of the wild type huPrP and the pathological mutant T183A. The differences in chemical shifts between the two variants reveal conformational alterations in some structural elements of the mutant, whereas the analyses of secondary shifts and random coil index provide indications on the putative mechanisms of misfolding of T183A huPrP.

Atomic force microscopy (AFM) imaging suggests that stromal interaction molecule 1 (STIM1) binds to Orai1 with sixfold symmetry

FEBS Letters ◽  
2014 ◽  
Vol 588 (17) ◽  
pp. 2874-2880 ◽  
Author(s):  
Dilshan Balasuriya ◽  
Shyam Srivats ◽  
Ruth D. Murrell-Lagnado ◽  
J. Michael Edwardson
Keyword(s):  
Atomic Force Microscopy ◽  
Force Microscopy ◽  
Stromal Interaction Molecule 1 ◽  
Atomic Force ◽  
Afm Imaging ◽  
Sixfold Symmetry

Imaging of Xenopus laevis Oocyte Plasma Membrane in Physiological-Like Conditions by Atomic Force Microscopy

2013 ◽  
Vol 19 (5) ◽  
pp. 1358-1363 ◽  
Author(s):  
Massimo Santacroce ◽  
Federica Daniele ◽  
Andrea Cremona ◽  
Diletta Scaccabarozzi ◽  
Michela Castagna ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Plasma Membrane ◽  
High Resolution ◽  
Membrane Proteins ◽  
Xenopus Laevis ◽  
Functional Study ◽  
Xenopus Laevis Oocyte ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Imaging

AbstractXenopus laevis oocytes are an interesting model for the study of many developmental mechanisms because of their dimensions and the ease with which they can be manipulated. In addition, they are widely employed systems for the expression and functional study of heterologous proteins, which can be expressed with high efficiency on their plasma membrane. Here we applied atomic force microscopy (AFM) to the study of the plasma membrane of X. laevis oocytes. In particular, we developed and optimized a new sample preparation protocol, based on the purification of plasma membranes by ultracentrifugation on a sucrose gradient, to perform a high-resolution AFM imaging of X. laevis oocyte plasma membrane in physiological-like conditions. Reproducible AFM topographs allowed visualization and dimensional characterization of membrane patches, whose height corresponds to a single lipid bilayer, as well as the presence of nanometer structures embedded in the plasma membrane and identified as native membrane proteins. The described method appears to be an applicable tool for performing high-resolution AFM imaging of X. laevis oocyte plasma membrane in a physiological-like environment, thus opening promising perspectives for studying in situ cloned membrane proteins of relevant biomedical/pharmacological interest expressed in this biological system.

scholarly journals Multiple regimes of operation in bimodal AFM: understanding the energy of cantilever eigenmodes

2013 ◽  
Vol 4 ◽  
pp. 385-393 ◽  
Author(s):  
Daniel Kiracofe ◽  
Arvind Raman ◽  
Dalia Yablon
Keyword(s):  
Single Frequency ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Imaging ◽  
Multiple Regimes ◽  
Nanoscale Imaging ◽  
Relative Kinetic ◽  
Series Of Experiments ◽  
Tapping Mode Afm ◽  
Afm Cantilever

One of the key goals in atomic force microscopy (AFM) imaging is to enhance material property contrast with high resolution. Bimodal AFM, where two eigenmodes are simultaneously excited, confers significant advantages over conventional single-frequency tapping mode AFM due to its ability to provide contrast between regions with different material properties under gentle imaging conditions. Bimodal AFM traditionally uses the first two eigenmodes of the AFM cantilever. In this work, the authors explore the use of higher eigenmodes in bimodal AFM (e.g., exciting the first and fourth eigenmodes). It is found that such operation leads to interesting contrast reversals compared to traditional bimodal AFM. A series of experiments and numerical simulations shows that the primary cause of the contrast reversals is not the choice of eigenmode itself (e.g., second versus fourth), but rather the relative kinetic energy between the higher eigenmode and the first eigenmode. This leads to the identification of three distinct imaging regimes in bimodal AFM. This result, which is applicable even to traditional bimodal AFM, should allow researchers to choose cantilever and operating parameters in a more rational manner in order to optimize resolution and contrast during nanoscale imaging of materials.

Atomic Force Microscopy (AFM) Imaging and Force Recognition at the Molecular Level in Bacteria

2004 ◽  
Vol 10 (S02) ◽  
pp. 1094-1095
Author(s):  
David P. Allison ◽  
Claretta J. Sullivan ◽  
Jennifer L. Morrell ◽  
Peter R. Hoyt ◽  
Mitchel J. Doktycz
Keyword(s):  
Atomic Force Microscopy ◽  
Molecular Level ◽  
Force Microscopy ◽  
Atomic Force ◽  
Afm Imaging

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

scholarly journals Structural effects of the highly protective V127 polymorphism on human prion protein

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Laszlo L. P. Hosszu ◽  
Rebecca Conners ◽  
Daljit Sangar ◽  
Mark Batchelor ◽  
Elizabeth B. Sawyer ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Structural Changes ◽  
Prion Diseases ◽  
Single Point ◽  
Structural Basis ◽  
Single Point Mutation ◽  
Solution Dynamics ◽  
Human Prion Protein ◽  
Prion Transmission

AbstractPrion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect remains unknown. Here we show that the mutation alters and constrains the PrP backbone conformation preceding the PrP β-sheet, stabilising PrP dimer interactions by increasing intermolecular hydrogen bonding. It also markedly changes the solution dynamics of the β2-α2 loop, a region of PrP structure implicated in prion transmission and cross-species susceptibility. Both of these structural changes may affect access to protein conformers susceptible to prion formation and explain its profound effect on prion disease.

scholarly journals How Microbes Use Force To Control Adhesion

2020 ◽  
Vol 202 (12) ◽  
Author(s):  
Albertus Viljoen ◽  
Johann Mignolet ◽  
Felipe Viela ◽  
Marion Mathelié-Guinlet ◽  
Yves F. Dufrêne
Keyword(s):  
Single Molecule ◽  
Molecular Mechanisms ◽  
Flow Chamber ◽  
Microbial Adhesion ◽  
Single Molecule Level ◽  
Force Microscopy ◽  
Atomic Force ◽  
Adhesive Interactions ◽  
And Function ◽  
Mechanisms Of Adhesion

ABSTRACT Microbial adhesion and biofilm formation are usually studied using molecular and cellular biology assays, optical and electron microscopy, or laminar flow chamber experiments. Today, atomic force microscopy (AFM) represents a valuable addition to these approaches, enabling the measurement of forces involved in microbial adhesion at the single-molecule level. In this minireview, we discuss recent discoveries made applying state-of-the-art AFM techniques to microbial specimens in order to understand the strength and dynamics of adhesive interactions. These studies shed new light on the molecular mechanisms of adhesion and demonstrate an intimate relationship between force and function in microbial adhesins.

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