Composition-driven Surface Domain Structuring Mediated by Sphingolipids and Membrane-active Proteins

Abstract

Biomembranes contain a wide variety of lipids and proteins within an essentially two-dimensional structure. The coexistence of such a large number of molecular species causes local tensions that frequently relax into a phase or compositional immiscibility along the lateral and transverse planes of the interface. As a consequence, a substantial microheterogeneity of the surface topography develops and that depends not only on the lipid-protein composition, but also on the lateral and transverse tensions generated as a consequence of molecular interactions. The presence of proteins, and immiscibility among lipids, constitute major perturbing factors for the membrane sculpturing both in terms of its surface topography and dynamics. In this work, we will summarize some recent evidences for the involvement of membrane-associated, both extrinsic and amphitropic, proteins as well as membrane-active phosphohydrolytic enzymes and sphingolipids in driving lateral segregation of phase domains thus determining long-range surface topography.

The immediate‐early oncoproteins Fra‐1, c‐Fos, and c‐Jun have distinguishable surface behavior and interactions with phospholipids

“…We have described in previous work that c‐Fos‐phospholipid interactions result in changes of packing,6, 60, 61 thus configuring a loop of effects with the above mentioned packing dependent molecular rearrangement of c‐Fos 62. Fra‐1 also induces changes in lipid packing, but in a very different way than c‐Fos (Gaggiotti, unpublished results), extending the biophysical molecular basis for discrimination between these closely related proteins.…”

Ablation of ceramide synthase 2 strongly affects biophysical properties of membranes

“…Such changes as reported herein may infl uence a variety of cellular functions, including activation/inhibition of specifi c signaling proteins that undergo conformational changes upon membrane physical alterations ( 28,29 ). Moreover, the existence of membrane domains with phase properties distinct from the bulk membrane is often associated with entrapment therein of ligands and receptors in order to amplify signal transduction ( 30 ) or to the activation of certain enzymes by facilitating their adsorption on the membrane at the interfacial defects between the two phases ( 31 ). In cell membranes, formation of such domains may occur transiently due to the constant lipid and protein reshuffl ing by cellular processes such as synthesis/degradation, fl ip-fl op, and traffi cking ( 32,33 ).…”

Sterol chemical configuration influences the thermotropic phase behaviour of dipalmitoylphosphatidylcholine bilayers containing 5α-cholestan-3β- and 3α-ol

“…Recent studies indicate that once the above biochemical processes are initiated, lipid raft reorganization occurs because of the demixing of the lipid constituents (Cremesti et al, 2002;Harder, 2003;Ramstedt and Slotte, 2006;Carpinteiro et al, 2008;Maggio et al, 2008;Goñi and Alonso, 2009) and the lateral redistribution of proteins and antigens on the membrane surface (Cremesti et al, 2002;Barenholz, 2004;Biasi et al, 2009). Some sterols, such as cholestanol, can effectively replace Chol in lipid rafts and still experience protein-induced lateral phase separation (Rosetti et al, 2010), whereas it is unclear whether desmosterol can behave in a similar manner (Huster et al, 2005;Vainio et al, 2006).…”