Pathological levels of glucosylceramide change the biophysical properties of artificial and cell membranes

2017 ◽  
Vol 19 (1) ◽  
pp. 340-346 ◽  
Author(s):  
Ana R. P. Varela ◽  
Ana E. Ventura ◽  
Ana C. Carreira ◽  
Aleksander Fedorov ◽  
Anthony H. Futerman ◽  
...  

Accumulation of glucosylceramide decreases membrane fluidity in artificial membranes and in cell models of Gaucher disease.

2021 ◽  
Author(s):  
Benjamin L Woods ◽  
Ian L Seim ◽  
Jessica Liu ◽  
Grace McLaughlin ◽  
Kevin S. Cannon ◽  
...  

Septin filaments build structures such as rings, lattices and gauzes that serve as platforms for localizing signaling and organizing cell membranes. How cells control the geometry of septin assemblies in poorly understood. We show here that septins are isodesmic polymers, in contrast to cooperative polymerization exhibited by F-actin and microtubules. We constructed a physical model to analyze and interpret how septin assemblies change in the presence of regulators in yeast extracts. Notably filaments differ in length and curvature in yeast extract compared to pure protein indicating cellular regulators modulate intrinsic biophysical features. Combining analysis of extracts from regulatory mutants with simulations, we found increased filament flexibility and reduced filament fragmentation promote assembly of septin rings, whereas reduced flexibility in crowded environments promotes local filament alignment. This work demonstrates how tuning of intrinsic features of septin filament assembly by regulatory proteins yields a diverse array of structures observed in cells.


2021 ◽  
Vol 35 (6) ◽  
Author(s):  
Bingen G. Monasterio ◽  
Noemi Jiménez‐Rojo ◽  
Aritz B. García‐Arribas ◽  
Howard Riezman ◽  
Félix M. Goñi ◽  
...  

2018 ◽  
Vol 399 (5) ◽  
pp. 447-452 ◽  
Author(s):  
Aleksandra Pavićević ◽  
Milan Lakočević ◽  
Milan Popović ◽  
Ana Popović-Bijelić ◽  
Marko Daković ◽  
...  

Abstract Gaucher disease (GD) is a lysosomal storage disorder, caused by an impaired function of β-glucocerebrosidase, which results in accumulation of glucocerebroside in cells, and altered membrane ordering. Using electron paramagnetic resonance spin labeling, a statistically significant difference in the order parameter between the peripheral blood mononuclear cell membranes of GD patients and healthy controls was observed. Moreover, the results show that the introduction of the enzyme replacement therapy leads to the restoration of the physiological membrane fluidity. Accordingly, this simple method could serve as a preliminary test for GD diagnosis and therapy efficiency.


Life Sciences ◽  
1985 ◽  
Vol 37 (15) ◽  
pp. 1403-1409 ◽  
Author(s):  
Bruce M. Cohen ◽  
George S. Zubenko

2021 ◽  
Author(s):  
G. Narahari Sastry ◽  
Nandan Kumar

Abstract Human cell membranes consist of various lipids that are essential for their structure and function. Several experimental techniques have been used to characterize the composition of human cell membranes; however, it is challenging task to depict in theoretical calculations. In this work, we have investigated the structure-function relationship of lipids in both homogeneous and heterogeneous bilayer models using Molecular-Dynamics to delineate the effect of heterogeneity on the biophysical properties of membranes. Results illustrated that the biophysical properties of heterogeneous membranes are dependent on the lipid composition and concentration. We observed that the presence of cholesterol in combination with other lipids, introduced compactness of the membrane, increasing the membrane thickness. The density of lipid head group, phosphate, and glycerol-ester in presence of cholesterol with or without sphingomyelin is an underlying reason for membrane ordering. The radial distribution function shows that the cholesterol, sphingomyelin and phosphatidylethanolamine self-interaction and the interaction between cholesterol and phosphatidylethanolamine determine the structure and function of the heterogeneous membrane. Our findings provide a baseline for membrane heterogeneity that would help in understanding the physiological properties of membranes and may help to wisely select the heterogeneous bilayer model to mimic the realistic human cell membranes and the associated phenomenon.


2016 ◽  
Author(s):  
Suranjana Sen ◽  
Seth R. Johnson ◽  
Yang Song ◽  
Sirisha Sirobhushanam ◽  
Ryan Tefft ◽  
...  

AbstractThe fatty acid composition of membrane glycerolipids is a major determinant ofStaphylococcus aureusmembrane biophysical properties that impacts key factors in cell physiology including susceptibility to membrane active antimicrobials, pathogenesis, and response to environmental stress. The fatty acids ofS. aureusare considered to be a mixture of branched-chain fatty acids (BCFAs), which increase membrane fluidity, and straight-chain fatty acids (SCFAs) that decrease it. The balance of BCFAs and SCFAs in strains USA300 and SH1000 was affected considerably by differences in the conventional laboratory medium in which the strains were grown with media such as Mueller-Hinton broth and Luria broth resulting in high BCFAs and low SCFAs, whereas growth in Tryptic Soy Broth and Brain-Heart Infusion broth led to reduction in BCFAs and an increase in SCFAs. Straight-chain unsaturated fatty acids (SCUFAs) were not detected. However, when the organism was grownex vivoin serum, the fatty acid composition was radically different with SCUFAs, which increase membrane fluidity, making up a substantial proportion of the total (<25%) with SCFAs (>37%) and BCFAs (>36%) making up the rest. Staphyloxanthin, an additional major membrane lipid component unique toS. aureus, tended to be greater in content in cells with high BCFAs or SCUFAs. Cells with high staphyloxanthin content had a lower membrane fluidity that was attributed to increased production of staphyloxanthin.S. aureussaves energy and carbon by utilizing host fatty acids for part of its total fatty acids when growing in serum. The fatty acid composition ofin vitrogrownS. aureusis likely to be a poor reflection of the fatty acid composition and biophysical properties of the membrane when the organism is growing in an infection in view of the role of SCUFAs in staphylococcal membrane composition and virulence.Funding:This work was funded in part by grant 1R15AI099977 to Brian Wilkinson and Craig Gatto and grant 1R15GM61583 to Craig Gatto from the National Institutes of Health


Lipids ◽  
1987 ◽  
Vol 22 (11) ◽  
pp. 820-823 ◽  
Author(s):  
Wim J. van Blitterswijk ◽  
Henk Hilkmann ◽  
Guy A. Storme

2014 ◽  
Vol 42 (5) ◽  
pp. 1401-1408 ◽  
Author(s):  
Félix M. Goñi ◽  
Jesús Sot ◽  
Alicia Alonso

Some of the simplest sphingolipids, namely sphingosine, ceramide and their phosphorylated compounds [sphingosine 1-phosphate (Sph-1-P) and ceramide 1-phosphate (Cer-1-P)], are potent metabolic regulators. Each of these lipids modifies in marked and specific ways the physical properties of the cell membranes, in what can be the basis for some of their physiological actions. The present paper is an overview of the mechanisms by which these sphingolipid signals, sphingosine and ceramide, in particular, are able to modify the properties of cell membranes.


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