Chapter 6 Cubic Membranes

Abstract

Biological membranes are among the most fascinating assemblies of biomolecules: a bilayer less than 10 nm thick, composed of rather small lipid molecules that are held together simply by noncovalent forces, defines the cell and discriminates between "inside" and "outside", survival, and death. Intracellular compartmentalization-governed by biomembranes as well-is a characteristic feature of eukaryotic cells, which allows them to fulfill multiple and highly specialized anabolic and catabolic functions in strictly controlled environments. Although cellular membranes are generally visualized as flat sheets or closely folded isolated objects, multiple observations also demonstrate that membranes may fold into "unusual", highly organized structures with 2D or 3D periodicity. The obvious correlation of highly convoluted membrane organizations with pathological cellular states, for example, as a consequence of viral infection, deserves close consideration. However, knowledge about formation and function of these highly organized 3D periodic membrane structures is scarce, primarily due to the lack of appropriate techniques for their analysis in vivo. Currently, the only direct way to characterize cellular membrane architecture is by transmission electron microscopy (TEM). However, deciphering the spatial architecture solely based on two-dimensionally projected TEM images is a challenging task and prone to artifacts. In this review, we will provide an update on the current progress in identifying and analyzing 3D membrane architectures in biological systems, with a special focus on membranes with cubic symmetry, and their potential role in physiological and pathophysiological conditions. Proteomics and lipidomics approaches in defined experimental cell systems may prove instrumental to understand formation and function of 3D membrane morphologies.

Birbeck Granule-Like “Organized Smooth Endoplasmic Reticulum” Resulting from the Expression of a Cytoplasmic YFP-Tagged Langerin

“…Of note, these latter OSER were stained by anti-protein disulfide isomerase, contrary to what we observed in our system. A remarkable feature of the YFP-Lang-induced OSER was topologic, as they appeared as stacks of membrane sheets that clearly did not display the symmetry and the periodicity of cubic membranes [12].…”

“…The formation of OSERs is largely dependent on the ability of ER resident membrane proteins to form multimers via their cytoplasmic tail [10], so the ability of GFP tag to form dimers explains its ability to induce OSER [4], [5]. Topologically, OSER induced by protein hyperexpression can be related to cubic membranes, which are highly convoluted membrane organizations displaying symmetries and 3-dimensional periodicities present in many biological systems [11], [12].…”

Early Dengue Virus Protein Synthesis Induces Extensive Rearrangement of the Endoplasmic Reticulum Independent of the UPR and SREBP-2 Pathway

“…The rearrangement and formation of virally-induced membrane structures have been reported for DENV and various positive-strand RNA viruses [2], [3], [4], [22], [23], [24], [25]. However, despite our improved understanding of the composition and three dimensional architecture of these structures, how they are formed, the requirements for their formation, the involvement of viral and host factors, and the induction of cellular pathways involved in lipid and ER biogenesis are still not well defined.…”

Why Do Membranes of Some Unhealthy Cells Adopt a Cubic Architecture?

“…Physicochemical exploration of phase diagrams of lipids in water, as well as the electron tomographical monitoring of biomembranes, has unveiled an unexpected dynamic diversity of structural organization. Changes in the lipid/protein inventory of cells—artificially engineered, associated with hunger, 1 or stress induced, 2,3 for instance, in the course of viral infection 4 —can cause conversion to these unusual spatial arrangements, specifically from lamellar bilayers to bicontinuous cubic lipid phases, referred to as cubic membranes. Of note, weak intermolecular interactions between distinct epitopes of biomembranes such as cytochrome b 5 or microsomal aldehyde dehydrogenase appear as a driving force toward appearance of these nanoperiodic structures.…”