scholarly journals The Cellular and Chemical Biology of Endocytic Trafficking and Intracellular Delivery—The GL–Lect Hypothesis

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3299
Author(s):  
Ludger Johannes
Keyword(s):  
Lipid Membranes ◽  
Tumor Targeting ◽  
Chemical Biology ◽  
Reverse Genetics ◽  
Lateral Diffusion ◽  
Intracellular Delivery ◽  
Membrane Bound ◽  
Delivery Strategies ◽  
Synthetic Approaches ◽  
Biology Research

Lipid membranes are common to all forms of life. While being stable barriers that delimitate the cell as the fundamental organismal unit, biological membranes are highly dynamic by allowing for lateral diffusion, transbilayer passage via selective channels, and in eukaryotic cells for endocytic uptake through the formation of membrane bound vesicular or tubular carriers. Two of the most abundant fundamental fabrics of membranes—lipids and complex sugars—are produced through elaborate chains of biosynthetic enzymes, which makes it difficult to study them by conventional reverse genetics. This review illustrates how organic synthesis provides access to uncharted areas of membrane glycobiology research and its application to biomedicine. For this Special Issue on Chemical Biology Research in France, focus will be placed on synthetic approaches (i) to study endocytic functions of glycosylated proteins and lipids according to the GlycoLipid–Lectin (GL–Lect) hypothesis, notably that of Shiga toxin; (ii) to mechanistically dissect its endocytosis and intracellular trafficking with small molecule; and (iii) to devise intracellular delivery strategies for immunotherapy and tumor targeting. It will be pointed out how the chemical biologist’s view on lipids, sugars, and proteins synergizes with biophysics and modeling to “look” into the membrane for atomistic scale insights on molecular rearrangements that drive the biogenesis of endocytic carriers in processes of clathrin-independent endocytosis.

scholarly journals Enzyme Catalysis Enhances Lateral Lipid Motility and Directional Particle Transport on Membranes

2021 ◽  
Author(s):  
Ambika Somasundar ◽  
Niladri Sekhar Mandal ◽  
Ayusman Sen
Keyword(s):  
Lipid Membranes ◽  
Enzyme Catalysis ◽  
Lateral Diffusion ◽  
Cholesterol Content ◽  
Supported Bilayers ◽  
Membrane Fluctuations ◽  
Diffusion Enhancement ◽  
Membrane Bound ◽  
Passive Tracers ◽  
Membrane Bound Enzymes

The dynamic interplay between the composition of lipid membranes and the behavior of membrane-bound enzymes is critical to the understanding of cellular function and viability, and the design of membrane-based biosensing platforms. While there is a significant body of knowledge on how lipid composition and dynamics affect membrane-bound enzymes, little is known about how enzyme catalysis influences the motility and lateral transport in lipid membranes. Using enzymes-attached lipids in supported bilayers (SLB), we show catalysis-induced enhanced lateral diffusion of lipids in the bilayer. Enhancing the membrane viscosity by increasing the cholesterol content in the bilayer suppresses the overall diffusion but not the relative diffusion enhancement of the enzyme-attached lipids. We also provide direct evidence of catalysis-induced membrane fluctuations leading to the enhanced diffusion of passive tracers resting on the SLB. Additionally, by using active enzyme patches, we demonstrate the directional transport of tracers on SLBs. These are first steps in understanding diffusion and transport in lipid membranes due to active, out-of-equilibrium processes that are the hallmark of living systems. In general, our study demonstrates how active enzymes can be used to control diffusion and transport in confined 2-D environments.

scholarly journals Reversible membrane deformations by straight DNA origami filaments

Soft Matter ◽  
2021 ◽  
Author(s):  
Henri G. Franquelim ◽  
Hendrik Dietz ◽  
Petra Schwille
Keyword(s):  
Lipid Membranes ◽  
Dna Origami ◽  
Membrane Bound ◽  
Membrane Deformations

Reversible MgCl2-induced blunt-end polymerization of membrane-bound straight DNA origami monomers into filaments leads to protruding deformations on freestanding lipid membranes.

scholarly journals Induction of Highly Curved Structures in Relation to Membrane Permeabilization and Budding by the Triterpenoid Saponins, α- and δ-Hederin

2013 ◽  
Vol 288 (20) ◽  
pp. 14000-14017 ◽  
Author(s):  
Joseph Lorent ◽  
Cécile S. Le Duff ◽  
Joelle Quetin-Leclercq ◽  
Marie-Paule Mingeot-Leclercq
Keyword(s):  
Lipid Membranes ◽  
Pore Formation ◽  
Lateral Diffusion ◽  
Molecular Shape ◽  
Membrane Curvature ◽  
Membrane Permeabilization ◽  
Spontaneous Curvature ◽  
Unilamellar Vesicles ◽  
Generalized Polarization ◽  
Triterpenoid Saponins

The interactions of triterpenoid monodesmosidic saponins, α-hederin and δ-hederin, with lipid membranes are involved in their permeabilizing effect. Unfortunately, the interactions of these saponins with lipid membranes are largely unknown, as are the roles of cholesterol or the branched sugar moieties (two for α-hederin and one for δ-hederin) on the aglycone backbone, hederagenin. The differences in sugar moieties are responsible for differences in the molecular shape of the saponins and the effects on membrane curvature that should be the most positive for α-hederin in a transbilayer direction. In large unilamellar vesicles and monocyte cells, we showed that membrane permeabilization was dependent on the presence of membrane cholesterol and saponin sugar chains, being largest for α-hederin and smallest for hederagenin. In the presence of cholesterol, α-hederin induced the formation of nonbilayer phases with a higher rate of Brownian tumbling or lateral diffusion. A reduction of Laurdan's generalized polarization in relation to change in order of the polar heads of phospholipids was observed. Using giant unilamellar vesicles, we visualized the formation of wrinkled borders, the decrease in liposome size, budding, and the formation of macroscopic pores. All these processes are highly dependent on the sugars linked to the aglycone, with α-hederin showing a greater ability to induce pore formation and δ-hederin being more efficient in inducing budding. Hederagenin induced intravesicular budding but no pore formation. Based on these results, a curvature-driven permeabilization mechanism dependent on the interaction between saponin and sterols and on the molecular shape of the saponin and its ability to induce local spontaneous curvature is proposed.

scholarly journals Electrodes modified with lipid membranes to study quinone oxidoreductases

2009 ◽  
Vol 37 (4) ◽  
pp. 707-712 ◽  
Author(s):  
Sophie A. Weiss ◽  
Lars J.C. Jeuken
Keyword(s):  
Lipid Membranes ◽  
Biochemical Properties ◽  
Model Membranes ◽  
Water Soluble ◽  
Enzyme Assays ◽  
Membrane Enzymes ◽  
Membrane Bound ◽  
Hydrophobic Nature

Quinone oxidoreductases are a class of membrane enzymes that catalyse the oxidation or reduction of membrane-bound quinols/quinones. The conversion of quinone/quinol by these enzymes is difficult to study because of the hydrophobic nature of the enzymes and their substrates. We describe some biochemical properties of quinones and quinone oxidoreductases and then look in more detail at two model membranes that can be used to study quinone oxidoreductases in a native-like membrane environment with their native lipophilic quinone substrates. The results obtained with these model membranes are compared with classical enzyme assays that use water-soluble quinone analogues.

Natural products-based chemical biology research on leukemic cell differentiation

2012 ◽  
Vol 42 (12) ◽  
pp. 1774-1780
Author(s):  
YingLi WU ◽  
ChuanXu LIU ◽  
GuoQiang CHEN ◽  
QianQian YIN
Keyword(s):  
Natural Products ◽  
Cell Differentiation ◽  
Chemical Biology ◽  
Leukemic Cell ◽  
Biology Research

Diffusion NMR and bicelle morphology

2011 ◽  
Vol 89 (9) ◽  
pp. 1021-1035 ◽  
Author(s):  
Peter M. Macdonald ◽  
Ronald Soong
Keyword(s):  
Lateral Diffusion ◽  
Diffusion Method ◽  
Nmr Studies ◽  
Diffusion Nmr ◽  
Magnetically Aligned Bicelles ◽  
Diffusion Studies ◽  
Membrane Bound ◽  
Nmr Diffusion ◽  
Pfg Nmr ◽  
Magnetically Aligned

This minireview focuses on diffusion NMR studies in bicelles. Following a discourse on diffusion fundamentals, and a comparative overview of fluorescence and NMR-based techniques for measuring diffusion, the pulsed field gradient (PFG) NMR diffusion method is introduced, emphasizing its specific advantages and limitations when applied to diffusion measurements in macroscopically oriented lamellar systems such as magnetically aligned bicelles. The utility of PFG NMR diffusion measurements in bicellar model membrane systems for examining lateral diffusion of membrane-bound molecular species is demonstrated, along with certain features of lateral diffusion that such studies illuminate. Further, those aspects of bicelle morphology that have been resolved using PFG NMR diffusion studies of various molecular weight soluble polymeric species are reviewed. The discussion concludes with an outline of future prospects for diffusion NMR studies in bicelles.

scholarly journals Construction of membrane-bound artificial cells using microfluidics: a new frontier in bottom-up synthetic biology

2016 ◽  
Vol 44 (3) ◽  
pp. 723-730 ◽  
Author(s):  
Yuval Elani
Keyword(s):  
Synthetic Biology ◽  
High Throughput ◽  
Lipid Membranes ◽  
Spatial Organization ◽  
Building Blocks ◽  
Artificial Cells ◽  
Bottom Up ◽  
Grand Challenges ◽  
New Frontier ◽  
Membrane Bound

The quest to construct artificial cells from the bottom-up using simple building blocks has received much attention over recent decades and is one of the grand challenges in synthetic biology. Cell mimics that are encapsulated by lipid membranes are a particularly powerful class of artificial cells due to their biocompatibility and the ability to reconstitute biological machinery within them. One of the key obstacles in the field centres on the following: how can membrane-based artificial cells be generated in a controlled way and in high-throughput? In particular, how can they be constructed to have precisely defined parameters including size, biomolecular composition and spatial organization? Microfluidic generation strategies have proved instrumental in addressing these questions. This article will outline some of the major principles underpinning membrane-based artificial cells and their construction using microfluidics, and will detail some recent landmarks that have been achieved.

scholarly journals 1,2,3-Triazoles: Synthesis and Biological Application

2020 ◽  
Author(s):  
Abdul Aziz Ali
Keyword(s):  
Drug Discovery ◽  
Supramolecular Chemistry ◽  
Organic Synthesis ◽  
Chemical Biology ◽  
Materials Science ◽  
Biological Activities ◽  
Fluorescent Imaging ◽  
Polymer Chemistry ◽  
Privileged Structure ◽  
Synthetic Approaches

Among nitrogen-containing heterocyclic compounds, 1,2,3-triazoles are privileged structure motif and received a great deal of attention in academics and industry. Even though absent in nature, 1,2,3-triazoles have found broad applications in drug discovery, organic synthesis, polymer chemistry, supramolecular chemistry, bioconjugation, chemical biology, fluorescent imaging, and materials science. Therefore, the development of facile and straightforward methodology for the synthesis of 1,2,3-triazoles is of noteworthy interest. In this study, emphasis will be given to numerous synthetic approaches for the synthesis of 1,2,3-triazoles, especially the popular click chemistry approach. Furthermore, several biological activities of this promising heterocycle will also be discussed.

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