Dynamic, yet structured: The cell membrane three decades after the Singer–Nicolson model

Abstract

The fluid mosaic membrane model proved to be a very useful hypothesis in explaining many, but certainly not all, phenomena taking place in biological membranes. New experimental data show that the compartmentalization of membrane components can be as important for effective signal transduction as is the fluidity of the membrane. In this work, we pay tribute to the Singer-Nicolson model, which is near its 30th anniversary, honoring its basic features, ''mosaicism'' and ''diffusion,'' which predict the interspersion of proteins and lipids and their ability to undergo dynamic rearrangement via Brownian motion. At the same time, modifications based on quantitative data are proposed, highlighting the often genetically predestined, yet flexible, multilevel structure implementing a vast complexity of cellular functions. This new ''dynamically structured mosaic model'' bears the following characteristics: emphasis is shifted from fluidity to mosaicism, which, in our interpretation, means nonrandom codistribution patterns of specific kinds of membrane proteins forming smallscale clusters at the molecular level and large-scale clusters (groups of clusters, islands) at the submicrometer level. The cohesive forces, which maintain these assemblies as principal elements of the membranes, originate from within a microdomain structure, where lipid-lipid, protein-protein, and protein-lipid interactions, as well as sub-and supramembrane (cytoskeletal, extracellular matrix, other cell) effectors, many of them genetically predestined, play equally important roles. The concept of fluidity in the original model now is interpreted as permissiveness of the architecture to continuous, dynamic restructuring of the molecular-and higherlevel clusters according to the needs of the cell and as evoked by the environment.

Ethyl-Eicosapentaenoic Acid in First-Episode Psychosis. A 1H-MRS Study

“…A recent study investigating T2 relaxation time the in vivo brain effects of omega-3 fatty acids using T2 relaxation time in patients with bipolar affective disorder supports preclinical findings that omega-3 fatty acids modulate membrane integrity (Hirashima et al, 2004), thereby potentially altering signal transduction and receptor binding (Vereb et al, 2003). One way to further investigate the potential in vivo brain effects of omega-3 fatty acids is proton magnetic resonance spectroscopy (1H-MRS), which can estimate regional concentrations of various brain metabolites.…”

Quantitative microscopy and systems biology: seeing the whole picture

“…It is now widely accepted that biological membranes are highly heterogeneous environments where the translational diVusion of proteins is restricted by various mechanisms (Vereb et al 2003). A good example is the clustering of molecules in membranes by mechanisms that may involve lipid-lipid, protein-protein and protein-lipid interactions.…”

“…A good example is the clustering of molecules in membranes by mechanisms that may involve lipid-lipid, protein-protein and protein-lipid interactions. The best know examples of such a phenomenon are lipid rafts that are deWned as small cholesterol-dependent domains in membranes in which certain proteins may aggregate (Lai 2003;Simons and Toomre 2000;Vereb et al 2003). It has been suggested that such domains may play a crucial role in signal transduction by sorting the signaling molecules and modifying their output properties by increasing their local concentrations (Lai 2003;Simons and Toomre 2000;Vereb et al 2003).…”

“…The best know examples of such a phenomenon are lipid rafts that are deWned as small cholesterol-dependent domains in membranes in which certain proteins may aggregate (Lai 2003;Simons and Toomre 2000;Vereb et al 2003). It has been suggested that such domains may play a crucial role in signal transduction by sorting the signaling molecules and modifying their output properties by increasing their local concentrations (Lai 2003;Simons and Toomre 2000;Vereb et al 2003). Lipid rafts have been This has been mainly due to a lack of proper experimental tools to study the formation and regulation of protein clusters at sub-micron spatial and millisecond temporal scales (Jacobson et al 2007).…”

Selecting the right fluorophores and flow cytometer for fluorescence resonance energy transfer measurements

“…The most apparent manifestation of the FRET process is the decrease of donor fluorescence in the presence of an acceptor in close vicinity (1-10 nm), which is accompanied by an increase of fluorescence of the acceptor (if the acceptor is a fluorescent molecule). The FRET phenomenon has been adapted for microscopy (3)(4)(5)(6) and flow cytometry (7)(8)(9) and several biological structures have been successfully investigated: receptors involved in immune response (10)(11)(12), growth factor receptors on tumor cells (13)(14)(15), determination of protein conformation (16,17), and lipid microdomain structures (9,18,19). Several reviews are also available for biomedical and clinical applications of FRET (8,18,(20)(21)(22)(23)(24).…”