Wade F. Zeno

Bio: Wade F. Zeno is an academic researcher from University of Texas at Austin. The author has contributed to research in topics: Membrane curvature & Membrane. The author has an hindex of 9, co-authored 20 publications receiving 377 citations. Previous affiliations of Wade F. Zeno include University of California, Davis & University of Southern California.

The 2018 biomembrane curvature and remodeling roadmap.

Abstract: The importance of curvature as a structural feature of biological membranes has been recognized for many years and has fascinated scientists from a wide range of different backgrounds. On the one hand, changes in membrane morphology are involved in a plethora of phenomena involving the plasma membrane of eukaryotic cells, including endo- and exocytosis, phagocytosis and filopodia formation. On the other hand, a multitude of intracellular processes at the level of organelles rely on generation, modulation, and maintenance of membrane curvature to maintain the organelle shape and functionality. The contribution of biophysicists and biologists is essential for shedding light on the mechanistic understanding and quantification of these processes. Given the vast complexity of phenomena and mechanisms involved in the coupling between membrane shape and function, it is not always clear in what direction to advance to eventually arrive at an exhaustive understanding of this important research area. The 2018 Biomembrane Curvature and Remodeling Roadmap of Journal of Physics D: Applied Physics addresses this need for clarity and is intended to provide guidance both for students who have just entered the field as well as established scientists who would like to improve their orientation within this fascinating area.

Synergy between intrinsically disordered domains and structured proteins amplifies membrane curvature sensing

Abstract: The ability of proteins to sense membrane curvature is essential to cellular function. All known sensing mechanisms rely on protein domains with specific structural features such as wedge-like amphipathic helices and crescent-shaped BAR domains. Yet many proteins that contain these domains also contain large intrinsically disordered regions. Here we report that disordered domains are themselves potent sensors of membrane curvature. Comparison of Monte Carlo simulations with in vitro and live-cell measurements demonstrates that the polymer-like behavior of disordered domains found in endocytic proteins drives them to partition preferentially to convex membrane surfaces, which place fewer geometric constraints on their conformational entropy. Further, proteins containing both structured curvature sensors and disordered regions are more than twice as curvature sensitive as their respective structured domains alone. These findings demonstrate an entropic mechanism of curvature sensing that is independent of protein structure and illustrate how structured and disordered domains can synergistically enhance curvature sensitivity.

BAR scaffolds drive membrane fission by crowding disordered domains.

Abstract: Cellular membranes are continuously remodeled. The crescent-shaped bin-amphiphysin-rvs (BAR) domains remodel membranes in multiple cellular pathways. Based on studies of isolated BAR domains in vitro, the current paradigm is that BAR domain–containing proteins polymerize into cylindrical scaffolds that stabilize lipid tubules. But in nature, proteins that contain BAR domains often also contain large intrinsically disordered regions. Using in vitro and live cell assays, here we show that full-length BAR domain–containing proteins, rather than stabilizing membrane tubules, are instead surprisingly potent drivers of membrane fission. Specifically, when BAR scaffolds assemble at membrane surfaces, their bulky disordered domains become crowded, generating steric pressure that destabilizes lipid tubules. More broadly, we observe this behavior with BAR domains that have a range of curvatures. These data suggest that the ability to concentrate disordered domains is a key driver of membrane remodeling and fission by BAR domain–containing proteins.

Molecular Mechanisms of Membrane Curvature Sensing by a Disordered Protein

Abstract: The ability of proteins to sense membrane curvature is essential for the initiation and assembly of curved membrane structures. Established mechanisms of curvature sensing rely on proteins with spe...

Fermentation Temperature Modulates Phosphatidylethanolamine and Phosphatidylinositol Levels in the Cell Membrane of Saccharomyces cerevisiae

Abstract: During alcoholic fermentation, Saccharomyces cerevisiae is exposed to a host of environmental and physiological stresses. Extremes of fermentation temperature have previously been demonstrated to induce fermentation arrest under growth conditions that would otherwise result in complete sugar utilization at "normal" temperatures and nutrient levels. Fermentations were carried out at 15°C, 25°C, and 35°C in a defined high-sugar medium using three Saccharomyces cerevisiae strains with diverse fermentation characteristics. The lipid composition of these strains was analyzed at two fermentation stages, when ethanol levels were low early in stationary phase and in late stationary phase at high ethanol concentrations. Several lipids exhibited dramatic differences in membrane concentration in a temperature-dependent manner. Principal component analysis (PCA) was used as a tool to elucidate correlations between specific lipid species and fermentation temperature for each yeast strain. Fermentations carried out at 35°C exhibited very high concentrations of several phosphatidylinositol species, whereas at 15°C these yeast strains exhibited higher levels of phosphatidylethanolamine and phosphatidylcholine species with medium-chain fatty acids. Furthermore, membrane concentrations of ergosterol were highest in the yeast strain that experienced stuck fermentations at all three temperatures. Fluorescence anisotropy measurements of yeast cell membrane fluidity during fermentation were carried out using the lipophilic fluorophore diphenylhexatriene. These measurements demonstrate that the changes in the lipid composition of these yeast strains across the range of fermentation temperatures used in this study did not significantly affect cell membrane fluidity. However, the results from this study indicate that fermenting S. cerevisiae modulates its membrane lipid composition in a temperature-dependent manner.

Physical Biology of the Cell

Abstract: Physical Biology of the Cell, 2nd Edition, is a textbook that focuses on the application of physical principles to understanding biological systems. The subject matter of the text is organized according to common physical principles that govern biological processes rather than in relation to the biological processes themselves, as is common for most biology and cell biology textbooks. Topics covered in the book span a broad range of interests, including electrostatics, molecular interactions, molecular motors and the cytoskeleton, and membranes. Each chapter features color figures, derived equations with relevant examples, and problem sets at the chapter’s conclusion. The problem sets at the end of the chapters are expanded from the first edition. Further, the second edition includes two new chapters, one on light and pattern formation, and another on the use of computation in exploring biological problems. Additional student and instructor resources are also available online. The primary audience for the textbook could include advanced undergraduate students or first-year graduate students. While the textbook may be best suited for a biophysics course, it could also be used as a primary or supplementary text for teaching cellular and molecular biology. As a teaching tool for cellular and molecular biology, the many examples featured throughout the text could easily be employed to assist students in learning the principles of how a cellular or molecular system functions. A basic level of mathematical proficiency would be required of the student. While this textbook could be an excellent resource for many courses, there are several topics commonly covered in biochemistry classes, such the glycolytic pathway, that are featured in the book but in different contexts than many widely used biochemistry texts. For a biophysics course that is heavily focused on techniques, individual references that discuss the specific techniques in detail would be more suitable than this book. Of course, any instructor seeking to use this textbook should be aware of its content before making a selection. This textbook is an excellent resource, both for a research scientist and for a teacher. The authors do a superb job of selecting the material for each chapter and explaining the material with equations and narrative in an easily digestible manner. Readers who enjoy this book may also enjoy Molecular Driving Forces by Dill and Bromberg, which gives excellent treatment of similar concepts.

Introduction To Statistical Thermodynamics

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Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

Abstract: Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.