Crystallization around solid-like nanosized docks can explain the specificity, diversity, and stability of membrane microdomains

Abstract

To date, it is widely accepted that microdomains do form in the biological membranes of all eukaryotic cells, and quite possibly also in prokaryotes. Those sub-micrometric domains play crucial roles in signaling, in intracellular transport, and even in inter-cellular communications. Despite their ubiquitous distribution, and the broad and lasting interest invested in those microdomains, their actual nature and composition, and even the physical rules that regiment their assembly still remain elusive and hotly debated. One of the most often considered models is the raft hypothesis, i.e., the partition of lipids between liquid disordered and ordered phases (Ld and Lo, respectively), the latter being enriched in sphingolipids and cholesterol. Although it is experimentally possible to obtain the formation of microdomains in synthetic membranes through Ld/Lo phase separation, there is an ever increasing amount of evidence, obtained with a wide array of experimental approaches, that a partition between domains in Ld and Lo phases cannot account for many of the observations collected in real cells. In particular, it is now commonly perceived that the plasma membrane of cells is mostly in Lo phase and recent data support the existence of gel or solid ordered domains in a whole variety of live cells under physiological conditions. Here, we present a model whereby seeds comprised of oligomerised proteins and/or lipids would serve as crystal nucleation centers for the formation of diverse gel/crystalline nanodomains. This could confer the selectivity necessary for the formation of multiple types of membrane domains, as well as the stability required to match the time frames of cellular events, such as intra- or inter-cellular transport or assembly of signaling platforms. Testing of this model will, however, require the development of new methods allowing the clear-cut discrimination between Lo and solid nanoscopic phases in live cells.

Formation and Properties of Membrane-Ordered Domains by Phytoceramide: Role of Sphingoid Base Hydroxylation

“…Thus it is conceivable that the abundance of sphingolipids with PhyCer backbone might be, at least in part, responsible for the stability of these gel domains in vivo, rendering them detectable with t-PnA fluorescence. This has, so far, not been reported for mammalian cells 38,57 . In particular, the sphingoid base hydroxylation provides the potential to form different types of highly ordered and rigid stoichiometric complexes that are stable under a large range of compositions and temperatures.…”

“…Several evidence concerning the formation of microdomains with distinct properties from mammalian 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 15 cells that do not fit the lipid raft definition, 57 both in plants and fungi, has been reported, and recently reviewed 9 . These include the presence of temporally and spatially stable compartments identified by fluorescence microscopy and fractions of immobile proteins during long periods of time that may reach hours or even during the whole cell cycle 9,58 .…”

Effects of Lateral and Terminal Chains of X-Shaped Bolapolyphiles with Oligo(phenylene ethynylene) Cores on Self-Assembly Behaviour. Part 1: Transition between Amphiphilic and Polyphilic Self-Assembly in the Bulk

“…The laterally attached alkyl chains (linear or branched) were expected to improve the compatibility of the rods with the alkyl chains of the phospholipids, whereas replacing the alkyl chains by semiperfluorinated chains is assumed to modify the interaction with the phospholipids [69,70]. If incorporated into lipid membranes, these X-shaped bolapolyphiles could provide membrane stabilization or destabilization (channel formation) [71], domain formation [72][73][74][75] and membrane compartmentalization [76] and might contribute to the knowledge about the effects of rod-like molecules (e.g., cholesterol) [75] or superstructures (α-helices of integral proteins) [77,78] on the membrane properties. Furthermore, ordered organizations of π-conjugated systems in lipid membranes are of potential interest for artificial light harvesting systems [79] and transmembrane electronic conduction [80].…”

Phospholipid/cholesterol/decanethiol mixtures for direct assembly of immunosensing interfaces

“…This fluidity will not only allow for the proper functional dynamics of the biosensing proteins but also facilitate the formation of a planar and continuous lipid bilayer from lipid vesicles. The liquid ordered phase is the most representative of plasma membrane in human cells and is very stable regarding temperature and pressure changes [25]. The lipid vesicles contain also 5% of decanethiol in order to promote a strong attachment of the lipid bilayer to the gold surface (Fig.…”