Fanani ML, Härtel S, De Tullio L, Jara J, Olmos F, Oliveira R & B Maggio
Biochimica et Biophysica Acta (BBA) – Biomembranes Volume 1798, Issue 7, 1309-1323

In recent years, new evidence in biomembrane research brought about a holistic, supramolecular view on membrane-mediated signal transduction. The consequences of sphingomyelinase (SMase) driven formation of ceramide (Cer) at the membrane interface involves reorganization of the lateral membrane structure of lipids and proteins from the nm to the ym level. In this review, we present recent insights about mechanisms and features of the SMase-mediated formation of Cer-enriched domains in model membranes, which have been elucidated through a combination of microscopic techniques with advanced image processing algorithms. This approach extracts subtle morphological and pattern information beyond the visual perception: since domain patterns are the consequences of subjacent biophysical properties, a reliable quantitative description of the supramolecular structure of the membrane domains yields a direct readout of biophysical properties which are difficult to determine otherwise. Most of the information about SMase action on simple lipid interfaces has arisen from monolayer studies, but the correspondence to lipid bilayer systems will also be discussed. Furthermore, the structural changes induced by sphingomyelinase action are not fully explained just by the presence of ceramide but by out-of equilibrium surface dynamics forcing the lipid domains to adopt transient supramolecular pattern with explicit interaction potentials. This rearrangement responds to a few basic physical properties like lipid mixing/demixing kinetics, electrostatic repulsion and line tension. The possible implications of such transient codes for signal transduction are discussed for SMase controlled action on lipid interfaces.

Acknowledgments: This work was supported in part by: SECyT-UNC, MinCyT (Prov. Córdoba), CONICET and FONCyT (Argentina); some aspects of this investigation are inscribed within the PAE 22642 network in Nanobiosciences. B.M., R.G.O. and M.L.F. are Career Investigators of CONICET; L.D. is a Doctoral Fellow of CONICET. Research in SCIAN-Lab (SH) is funded by FONDECYT (1090246) and FONDEF (D07I1019), the Millennium Scientific Initiative (ICM P04-068-F). SCIAN-Lab is a selected member of the German-Chilean Center of Excellence Initiative for Medical Informatics (DAAD). JJ is funded by a PhD scholarship from CONICYT (Chile). FO is funded by FONDECYT (1090246), FONDEF (D07I1019) and Proyecto Bicentenario R18. The Authors thank N. Contreras from Area Kreativa for support with the figures.

Download PDF