scholarly journals Polyglutamine aggregates impair lipid membrane integrity and enhance lipid membrane rigidity

2016 ◽  
Vol 1858 (4) ◽  
pp. 661-670 ◽  
Author(s):  
Chian Sing Ho ◽  
Nawal K. Khadka ◽  
Fengyu She ◽  
Jianfeng Cai ◽  
Jianjun Pan
Keyword(s):  
Lipid Membrane ◽  
Membrane Integrity ◽  
Membrane Rigidity

scholarly journals The interplay between lipids and dopamine on α-synuclein oligomerization and membrane binding

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Chi L. L. Pham ◽  
Roberto Cappai
Keyword(s):  
Lipid Membranes ◽  
Amyloid Fibrils ◽  
Lipid Membrane ◽  
Hydrophobic Interactions ◽  
Membrane Integrity ◽  
Lipid Vesicles ◽  
Helical Conformation ◽  
Unfolded Protein ◽  
Natively Unfolded Protein ◽  
Natively Unfolded

The deposition of α-syn (α-synuclein) as amyloid fibrils and the selective loss of DA (dopamine) containing neurons in the substantia nigra are two key features of PD (Parkinson's disease). α-syn is a natively unfolded protein and adopts an α-helical conformation upon binding to lipid membrane. Oligomeric species of α-syn have been proposed to be the pathogenic species associated with PD because they can bind lipid membranes and disrupt membrane integrity. DA is readily oxidized to generate reactive intermediates and ROS (reactive oxygen species) and in the presence of DA, α-syn form of SDS-resistant soluble oligomers. It is postulated that the formation of the α-syn:DA oligomers involves the cross-linking of DA-melanin with α-syn, via covalent linkage, hydrogen and hydrophobic interactions. We investigate the effect of lipids on DA-induced α-syn oligomerization and studied the ability of α-syn:DA oligomers to interact with lipids vesicles. Our results show that the interaction of α-syn with lipids inhibits the formation of DA-induced α-syn oligomers. Moreover, the α-syn:DA oligomer cannot interact with lipid vesicles or cause membrane permeability. Thus, the formation of α-syn:DA oligomers may alter the actions of α-syn which require membrane association, leading to disruption of its normal cellular function.

Alteration of Lipid Membrane Rigidity by Cholesterol and Its Metabolic Precursors

2005 ◽  
Vol 219 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Horia I. Petrache ◽  
Daniel Harries ◽  
V. Adrian Parsegian
Keyword(s):  
Lipid Membrane ◽  
Membrane Rigidity ◽  
Metabolic Precursors

Preservation of Supported Lipid Membrane Integrity from Thermal Disruption: Osmotic Effect

2016 ◽  
Vol 8 (9) ◽  
pp. 5857-5866
Author(s):  
Tao Zhu ◽  
Zhongying Jiang ◽  
Yuqiang Ma ◽  
Yong Hu
Keyword(s):  
Lipid Membrane ◽  
Membrane Integrity ◽  
Osmotic Effect

scholarly journals Influence of Lipid Membrane Rigidity on Properties of Supporting Polymer

2011 ◽  
Vol 101 (1) ◽  
pp. 128-133 ◽  
Author(s):  
Michael S. Jablin ◽  
Manish Dubey ◽  
Mikhail Zhernenkov ◽  
Ryan Toomey ◽  
Jarosław Majewski
Keyword(s):  
Lipid Membrane ◽  
Membrane Rigidity

scholarly journals 1-Deoxysphingolipids Tempt Autophagy Resulting in Lysosomal Lipid Substrate Accumulation: Tracing the Impact of 1-Deoxysphingolipids on Ultra-Structural Level using a Novel Click-Chemistry Detection

2021 ◽  
Author(s):  
Christian Lamberz ◽  
Marina Hesse ◽  
Gregor Kirfel
Keyword(s):  
Energy Homeostasis ◽  
Lipid Membrane ◽  
Membrane Damage ◽  
Membrane Integrity ◽  
Membrane Dynamics ◽  
Autophagic Flux ◽  
Structural Level ◽  
Cellular Energy ◽  
The Impact ◽  
Lipid Substrate

SUMMARYSphingolipids (SLs) are pivotal components of biological membranes essentially contributing to their physiological functions. 1-deoxysphingolipids (deoxySLs), an atypical cytotoxic acting sub-class of SLs, is relevant for cellular energy homeostasis and is known to be connected to neurodegenerative disorders including diabetic neuropathy and hereditary sensory neuropathy type 1 (HSAN1). High levels of deoxySLs affect lipid membrane integrity in artificial liposomes. Accordingly, recent reports questioned the impact of deoxySLs on physiological lipid membrane and organelle functions leading to impaired cellular energy homeostasis.However, DeoxySL-related structural effects on cell membranes resulting in organelle dysfunction are still obscure. To illuminate disease-relevant sub-cellular targets of deoxySLs, we traced alkyne-containing 1-deoxysphinganine (alkyne-DOXSA) and resulting metabolites on ultra-structural level using a new labeling approach for electron microscopy (EM) termed “Golden-Click-Method” (GCM). To complement high-resolution analysis with membrane dynamics, selected intracellular compartments were traced using fluorescent live dyes.Our results conclusively linked accumulating cytotoxic deoxySLs with mitochondria and endoplasmic reticulum (ER) damage triggering Autophagy of mitochondria and membrane cisterna of the ER. The induced autophagic flux ultimately leads to accumulating deoxySL containing intra-lysosomal lipid crystals. Lysosomal lipid substrate accumulation impaired physiological lysosome functions and caused cellular starvation. Lysosomal exocytosis appeared as a mechanism for cellular clearance of cytotoxic deoxySLs. In sum, our data define new ultra-structural targets of deoxySLs and link membrane damage to autophagy and abnormal lysosomal lipid accumulation. These insights may support new conclusions about diabetes type 2 and HSNA1 related tissue damage.

scholarly journals Stiffness of fluid and gel phase lipid nanovesicles: weighting the contributions of membrane bending modulus and luminal pressurization

2021 ◽  
Author(s):  
Andrea Ridolfi ◽  
Lucrezia Caselli ◽  
Matteo Baldoni ◽  
Costanza Montis ◽  
Francesco Mercuri ◽  
...  
Keyword(s):  
Mechanical Response ◽  
Lipid Membrane ◽  
Dominant Role ◽  
Fluid Phase ◽  
Lipid Vesicles ◽  
Unified Model ◽  
Coarse Grained ◽  
Bending Modulus ◽  
Membrane Rigidity ◽  
Gel Phase

The mechanical properties of biogenic membranous compartments are thought to be relevant in numerous biological processes; however, their quantitative measurement remains challenging for most of the already available Force Spectroscopy (FS)-based techniques. In particular, the debate on the mechanics of lipid nanovesicles and on the interpretation of their mechanical response to an applied force is still open. This is mostly due to the current lack of a unified model being able to describe the mechanical response of gel and fluid phase lipid vesicles and to disentangle the contributions of membrane rigidity and luminal pressure. In this framework, we herein propose a simple model in which the contributions of membrane rigidity and luminal pressure to the overall vesicle stiffness are described as a series of springs; this approach allows estimating the two contributions for both gel and fluid phase liposomes. Atomic Force Microscopy-based FS (AFM-FS), performed on both vesicles and Supported Lipid Bilayers (SLBs), is exploited for obtaining all the parameters involved in the model. Moreover, the use of coarse-grained full-scale molecular dynamics simulations allowed for better understanding the differences in the mechanical responses of gel and fluid phase bilayers and supported the experimental findings. Results suggest that the pressure contribution is similar among all the probed vesicle types; however, it plays a dominant role in the mechanical response of lipid nanovesicles presenting a fluid phase membrane, while its contribution becomes comparable to the one of membrane rigidity in nanovesicles with a gel phase lipid membrane. The herein presented results offer a simple way to quantify two of the most important parameters in vesicular nanomechanics, and as such represent a first step towards a currently unavailable, unified model for the mechanical response of gel and fluid phase lipid nanovesicles.

scholarly journals 3D-Visualization of Amyloid-β Oligomer and Fibril Interactions with Lipid Membranes by Cryo-Electron Tomography

2020 ◽  
Author(s):  
Yao Tian ◽  
Ruina Liang ◽  
Amit Kumar ◽  
Piotr Szwedziak ◽  
John H. Viles
Keyword(s):  
Lipid Bilayers ◽  
Molecular Mechanisms ◽  
Lipid Membrane ◽  
Electron Tomography ◽  
3D Visualization ◽  
Membrane Integrity ◽  
Amyloid Β ◽  
Lipid Vesicles ◽  
Aβ Oligomers ◽  
Cryo Electron Tomography

ABSTRACTAmyloid-β (Aβ) monomers assemble into mature fibrils via a range of metastable oligomeric and protofibrillar intermediates. These Aβ assemblies have been shown to bind to lipid bilayers. This can disrupt membrane integrity and cause a loss of cellular homeostasis, that triggers a cascade of events leading to Alzheimer’s disease. However, molecular mechanisms of Aβ cytotoxicity and how the different assembly forms interact with the membrane remain enigmatic. Here we use cryo-electron tomography (cryoET) to obtain three-dimensional nano-scale images of various Aβ assembly types and their interaction with liposomes. Aβ oligomers bind extensively to the lipid vesicles, inserting and carpeting the upper-leaflet of the bilayer. Furthermore, curvilinear protofibrils also insert into the bilayer, orthogonally to the membrane surface. Aβ oligomers concentrate at the interface of vesicles and form a network of Aβ-linked liposomes. While crucially, monomeric and fibrillar Aβ have relatively little impact on the membrane. Changes to lipid membrane composition highlights a significant role for GM1-ganglioside in promoting Aβ-membrane interactions. The different effects of Aβ assembly forms observed align with the highlighted cytotoxicity reported for Aβ oligomers. The wide-scale incorporation of Aβ oligomers and curvilinear protofibrils into the lipid bilayer suggests a mechanism by which membrane integrity is lost.

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