Dynamic pattern generation in cell membranes: Current insights into membrane organization

Abstract

It has been two decades since the lipid raft hypothesis was first presented. Even today, whether these nanoscale cholesterol-rich domains are present in cell membranes is not completely resolved. However, especially in the last few years, a rich body of literature has demonstrated both the presence and the importance of non-random distribution of biomolecules on the membrane, which is the focus of this review. These new developments have pushed the experimental limits of detection and have brought us closer to observing lipid domains in the plasma membrane of live cells. Characterization of biomolecules associated with lipid rafts has revealed a deep connection between biological regulation and function and membrane compositional heterogeneities. Finally, tantalizing new developments in the field have demonstrated that lipid domains might not just be associated with the plasma membrane of eukaryotes but could potentially be a ubiquitous membrane-organizing principle in several other biological systems. This article is part of a Special Issue entitled: Emergence of Complex Behavior in Biomembranes edited by Marjorie Longo.

Imaging FCS Delineates Subtle Heterogeneity in Plasma Membranes of Resting Mast Cells

“…Considerable evidence supports the view that nanoscale Lo-like channels align along the picket fences, either by the effects of critical behavior and pinned Lo-preferring components (30,31,34) or by stabilization with Lo-preferring protein pickets (35,36). In the hierarchical model, Lo-like nanodomains (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) nm) and protein complexes (3-10 nm) also exist within the corrals. In addition, experiments and simulations underlying the active composite model of Mayor, Rao, and colleagues showed that ordered lipid nanodomains also arise from active, myosin-driven asters of short actin chains that connect to inner leaflet lipids and cause alignment of tails of Lo-preferring lipids in the outer leaflet (37)(38)(39).…”

“…A prominent example is "lipid rafts," an ill-defined term for dynamic proteolipid nanodomains that resemble the liquid ordered (Lo) phase in model membranes (8). Although there is ample experimental support for participation of these Lo-like proteolipid nanodomains (a term we currently prefer to "rafts") in stimulated signaling (7,(9)(10)(11)(12)(13), their physical nature has been difficult to define because of their diversity, their sub-resolution dimensions, and their transience (12)(13)(14)(15)(16)(17)(18)(19). Over the years we have used a wide range of approaches to examine these nanodomains because of their clear participation in transmembrane signaling initiated by the high affinity receptor (FcεRI) for immunoglobulin E (IgE) on mast cells, as triggered by multivalent antigen in the allergic immune response (20).…”

Mechanical activation of TWIK-related potassium channel by nanoscopic movement and rapid second messenger signaling

“…After shearing, cells were fixed, stained, and imaged identically to static samples with dSTORM. (b) Recent research has shown variability in the detection of domains in cells based on technique and labeling molecules 29,64,65 . Because of its pentavalent nature, CTxB has been suggested to induce lipid rafts post-fixation due to the idea that lipids remain mobile after fixation.…”

MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?

“…Spatiotemporal organization of biological membranes is characterized by dynamic lateral heterogeneity, as proven by many biophysical and biochemical observations. One of the best known and most acknowledged forms of this heterogeneity is the existence of lateral subcompartments, called membrane rafts (lipid rafts) -a concept formulated by Simons and Ikonen in 1997 [9] which has been the subject of detailed current reviews [10][11][12].…”

“…For example, the raft domain is suggested to be a site for HIV budding, binding [32] and stabilization of rafts by cholera toxin (Ctx) and Shiga toxin (Stx) [33,34]. Also VacA, a vacuolating toxin of H. pylori, predominantly associates with the raft phase; however, this binding was found to be independent of oligomerization and pore-forming activity [10,35]. For example, an interesting observation was published recently indicating that H. pylori expression of the cgt gene encoding cholesterol-a-glucosyltransferase reduces cholesterol levels in infected gastric epithelial cells, which disrupts membrane rafts, blocking in turn IFNg signaling, allowing bacteria to escape the host inflammatory response [36].…”