scholarly journals Biomechanical control of lysosomal secretion via the VAMP7 hub: a tug-of-war mechanism between VARP and LRRK1

2017 ◽  
Author(s):  
Guan Wang ◽  
Sébastien Nola ◽  
Simone Bovio ◽  
Maïté Coppey-Moisan ◽  
Frank Lafont ◽  
...  
Keyword(s):  
Membrane Dynamics ◽  
Interacting Protein ◽  
Force Microscopy ◽  
Mechanical Constraints ◽  
Readily Releasable Pool ◽  
Atomic Force ◽  
Substrate Rigidity ◽  
Secretory Lysosome ◽  
Biomechanical Constraints ◽  
Secretory Lysosomes

AbstractThe rigidity of the cell environment can vary tremendously between tissues and in pathological conditions. How this property may affect intracellular membrane dynamics is still largely unknown. Here, using atomic force microscopy, we found that cells deficient in the secretory lysosome v-SNARE VAMP7 were impaired in adapting to substrate rigidity. Conversely VAMP7-mediated secretion was stimulated by more rigid substrate and this regulation depended on the Longin domain of VAMP7. We further found that the Longin domain bound the kinase and retrograde trafficking adaptor LRRK1 and LRRK1 negatively regulated VAMP7-mediated exocytosis. Conversely, VARP, a VAMP7- and kinesin 1-interacting protein, further controlled the availability for secretion of peripheral VAMP7 vesicles and response of cells to mechanical constraints. We propose a mechanism whereby biomechanical constraints regulate VAMP7- dependent lysosomal secretion via LRRK1 and VARP tug-of-war control of the peripheral readily- releasable pool of secretory lysosomes.

scholarly journals Human Polymerase δ-Interacting Protein 2 (PolDIP2) Inhibits the Formation of Human Tau Oligomers and Fibrils

2021 ◽  
Vol 22 (11) ◽  
pp. 5768
Author(s):  
Kazutoshi Kasho ◽  
Lukas Krasauskas ◽  
Vytautas Smirnovas ◽  
Gorazd Stojkovič ◽  
Ludmilla A. Morozova-Roche ◽  
...  
Keyword(s):  
Dot Blot ◽  
Interacting Protein ◽  
Force Microscopy ◽  
Tau Oligomers ◽  
Atomic Force ◽  
Central Characteristic ◽  
Tau Aggregation ◽  
Dot Blot Analysis ◽  
The Brain

A central characteristic of Alzheimer’s disease (AD) and other tauopathies is the accumulation of aggregated and misfolded Tau deposits in the brain. Tau-targeting therapies for AD have been unsuccessful in patients to date. Here we show that human polymerase δ-interacting protein 2 (PolDIP2) interacts with Tau. With a set of complementary methods, including thioflavin-T-based aggregation kinetic assays, Tau oligomer-specific dot-blot analysis, and single oligomer/fibril analysis by atomic force microscopy, we demonstrate that PolDIP2 inhibits Tau aggregation and amyloid fibril growth in vitro. The identification of PolDIP2 as a potential regulator of cellular Tau aggregation should be considered for future Tau-targeting therapeutics.

Stressed States and Self-Organized Structuring of W/C Multilayers

2001 ◽  
Vol 695 ◽  
Author(s):  
D.C. Meyer ◽  
A. Klingner ◽  
T. Leisegang ◽  
Th. Holz ◽  
R. Dietsch ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Mechanical Stability ◽  
Point Of View ◽  
Mountain Range ◽  
X Ray ◽  
Force Microscopy ◽  
Additional Information ◽  
Mechanical Constraints ◽  
Self Organized ◽  
Atomic Force

ABSTRACTCharacterization and quantitative analysis of stressed states of a series of W/C multilayers (10-40 periods prepared by pulsed laser deposition on Si (111) substrates of different thickness) were carried out by means of X-ray reflectometry, wide angle diffractometry and a novel laser mapping device. As the W/C multilayers were dedicated to technical applications as X-ray optics and subjected to optimization of stacking parameters (thickness and number of layers) for a long term (mechanical) stability also further investigations will be discussed. Comparison of wafer distortion as evaluated by laser scanning and strain of the W layer as deduced from X-ray diffraction let us conclude that W layers are under compressive and C layers under tensile stress. The investigation of the thermally stimulated relaxation behavior of the multilayers provided a confirmation of these results. Additional information could be obtained by comparative relaxation experiments under external mechanical constraints. Furthermore, we report on a self-organized process of structuring of the multilayers under investigation, which might be of interest also from a technical point of view. The entire surface area (diameter 2') could be converted from the smooth (as-deposited) to a structured (relaxed) state stable at room temperature. Investigations using optical and atomic force microscopy showed that the topology of the surface consists of a mountain range where the valleys are on the level of the as-deposited non-debonded surface and that long wrinkled ridges of about the same height run along arbitrary directions.

scholarly journals RIP3-mediated necroptosis is regulated by inter-filament assembly of RIP homotypic interaction motif

2020 ◽  
Vol 28 (1) ◽  
pp. 251-266 ◽  
Author(s):  
Hong Hu ◽  
Xialian Wu ◽  
Guoxiang Wu ◽  
Ning Nan ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Formation ◽  
Wild Type ◽  
Interacting Protein ◽  
Kinase Activation ◽  
Force Microscopy ◽  
Filament Assembly ◽  
Atomic Force ◽  
Homotypic Interaction ◽  
Mutual Antagonism

AbstractNecroptosis is mediated by signaling complexes called necrosomes, which contain receptor-interacting protein 3 (RIP3) and upstream effectors, such as RIP1. In necrosomes, the RIP homotypic interaction motif (RHIM) of RIP3 and RIP1 forms amyloidal complex. But how the amyloidal necrosomes control RIP3 activation and cell necroptosis has not been determined. Here, we showed that RIP3 amyloid fibrils could further assemble into large fibrillar networks which presents as cellular puncta during necroptosis. A viral RHIM-containing necroptosis inhibitor M45 could form heteroamyloid with RIP3 in cells and prevent RIP3 puncta formation and cell necroptosis. We characterized mutual antagonism between RIP3–RHIM and M45–RHIM in necroptosis regulation, which was caused by distinct inter-filament interactions in RIP3, M45 amyloids revealed with atomic force microscopy. Moreover, double mutations Asn464 and Met468 in RIP3–RHIM to Asp disrupted RIP3 kinase-dependent necroptosis. While the mutant RIP3(N464D/M468D) could form amyloid as wild type upon necroptosis induction. Based on these results, we propose that RIP3 amyloid formation is required but not sufficient in necroptosis signaling, the ordered inter-filament assembly of RIP3 is critical in RIP3 amyloid mediated kinase activation and cell necroptosis.

scholarly journals Non-Invasive Imaging of Membrane Dynamics Accompanied with Endocytosis in Living Cells by Atomic Force Microscopy

2016 ◽  
Vol 110 (3) ◽  
pp. 594a
Author(s):  
Aiko Yoshida ◽  
Shuichi Ito ◽  
Masahiro Kumeta ◽  
Shige H. Yoshimura
Keyword(s):  
Atomic Force Microscopy ◽  
Living Cells ◽  
Membrane Dynamics ◽  
Force Microscopy ◽  
Non Invasive ◽  
Atomic Force

Cryogenic atomic force microscopy

1991 ◽  
Vol 49 ◽  
pp. 54-55
Author(s):  
K. A. Fisher ◽  
M. G. L. Gustafsson ◽  
M. B. Shattuck ◽  
J. Clarke
Keyword(s):  
Room Temperature ◽  
Rapid Freezing ◽  
Cryogenic Temperatures ◽  
Soft Or ◽  
Electrically Conductive ◽  
Force Microscopy ◽  
Flexible Molecules ◽  
Advantages And Disadvantages ◽  
Atomic Force ◽  
Chemical Perturbation

The atomic force microscope (AFM) is capable of imaging electrically conductive and non-conductive surfaces at atomic resolution. When used to image biological samples, however, lateral resolution is often limited to nanometer levels, due primarily to AFM tip/sample interactions. Several approaches to immobilize and stabilize soft or flexible molecules for AFM have been examined, notably, tethering coating, and freezing. Although each approach has its advantages and disadvantages, rapid freezing techniques have the special advantage of avoiding chemical perturbation, and minimizing physical disruption of the sample. Scanning with an AFM at cryogenic temperatures has the potential to image frozen biomolecules at high resolution. We have constructed a force microscope capable of operating immersed in liquid n-pentane and have tested its performance at room temperature with carbon and metal-coated samples, and at 143° K with uncoated ferritin and purple membrane (PM).

AFM study of the dynamics of α-alumina surface faceting during high-temperature processing

1995 ◽  
Vol 53 ◽  
pp. 334-335 ◽  
Author(s):  
Michael W. Bench ◽  
Jason R. Heffelfinger ◽  
C. Barry Carter
Keyword(s):  
High Temperature ◽  
Thin Foil ◽  
Sem Analysis ◽  
Conductive Coatings ◽  
Force Microscopy ◽  
Minimal Sample ◽  
Atomic Force ◽  
Formation And Evolution ◽  
High Temperature Processing ◽  
Nominal Surface

To gain a better understanding of the surface faceting that occurs in α-alumina during high temperature processing, atomic force microscopy (AFM) studies have been performed to follow the formation and evolution of the facets. AFM was chosen because it allows for analysis of topographical details down to the atomic level with minimal sample preparation. This is in contrast to SEM analysis, which typically requires the application of conductive coatings that can alter the surface between subsequent heat treatments. Similar experiments have been performed in the TEM; however, due to thin foil and hole edge effects the results may not be representative of the behavior of bulk surfaces.The AFM studies were performed on a Digital Instruments Nanoscope III using microfabricated Si3N4 cantilevers. All images were recorded in air with a nominal applied force of 10-15 nN. The alumina samples were prepared from pre-polished single crystals with (0001), , and nominal surface orientations.

Scanning tunneling microscopy and atomic force microscopy: New tools for biology

1989 ◽  
Vol 47 ◽  
pp. 778-779
Author(s):  
CE Bracker ◽  
P. K. Hansma
Keyword(s):  
Physical Property ◽  
Scanning Probe ◽  
Scanning Tunneling ◽  
Small Scale ◽  
Tunneling Microscopy ◽  
Force Microscopy ◽  
New Family ◽  
Small Probe ◽  
Atomic Force ◽  
Transmission Electron

A new family of scanning probe microscopes has emerged that is opening new horizons for investigating the fine structure of matter. The earliest and best known of these instruments is the scanning tunneling microscope (STM). First published in 1982, the STM earned the 1986 Nobel Prize in Physics for two of its inventors, G. Binnig and H. Rohrer. They shared the prize with E. Ruska for his work that had led to the development of the transmission electron microscope half a century earlier. It seems appropriate that the award embodied this particular blend of the old and the new because it demonstrated to the world a long overdue respect for the enormous contributions electron microscopy has made to the understanding of matter, and at the same time it signalled the dawn of a new age in microscopy. What we are seeing is a revolution in microscopy and a redefinition of the concept of a microscope.Several kinds of scanning probe microscopes now exist, and the number is increasing. What they share in common is a small probe that is scanned over the surface of a specimen and measures a physical property on a very small scale, at or near the surface. Scanning probes can measure temperature, magnetic fields, tunneling currents, voltage, force, and ion currents, among others.

Morphology and development of flow-pattern defect with extended nonagitated Secco etching

1994 ◽  
Vol 52 ◽  
pp. 868-869
Author(s):  
Y. Pan
Keyword(s):  
Flow Pattern ◽  
Silicon Crystal ◽  
Gate Oxide ◽  
Crystal Growth Rate ◽  
Etch Depth ◽  
Force Microscopy ◽  
Etch Pit ◽  
Float Zone ◽  
Atomic Force ◽  
Multiple Step

The D defect, which causes the degradation of gate oxide integrities (GOI), can be revealed by Secco etching as flow pattern defect (FPD) in both float zone (FZ) and Czochralski (Cz) silicon crystal or as crystal originated particles (COP) by a multiple-step SC-1 cleaning process. By decreasing the crystal growth rate or high temperature annealing, the FPD density can be reduced, while the D defectsize increased. During the etching, the FPD surface density and etch pit size (FPD #1) increased withthe etch depth, while the wedge shaped contours do not change their positions and curvatures (FIG.l).In this paper, with atomic force microscopy (AFM), a simple model for FPD morphology by non-crystallographic preferential etching, such as Secco etching, was established.One sample wafer (FPD #2) was Secco etched with surface removed by 4 μm (FIG.2). The cross section view shows the FPD has a circular saucer pit and the wedge contours are actually the side surfaces of a terrace structure with very small slopes. Note that the scale in z direction is purposely enhanced in the AFM images. The pit dimensions are listed in TABLE 1.

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