RESUMEN
Ceramides are an important group of sphingolipids that modulate several cellular events. The mechanisms underlying biological actions of ceramides are not fully known, but evidence suggests that ceramides can act through regulation of the biophysical properties of the membrane. However, ceramide-induced changes on membrane properties are complex and depend on several factors. To gain further insight into this subject, we characterized the biophysical impact of very-long acyl chain C24-ceramide in a fluid model membrane under thermodynamic equilibrium and non-equilibrium conditions. Our results show that C24-ceramide readily forms two types of gel domains with distinct properties, likely corresponding to different interdigitated metastable gel phases. Upon reaching thermodynamic equilibrium, only partially interdigitated gel phase coexists with the fluid phase. In addition, C24-ceramide promotes strong changes in the shape of the vesicles, including domains with sharp edges and tubule-like structures. The results suggest that the formation of very long acyl chain ceramides in response to stress stimuli will initially induce a multitude of changes in the organization and fluidity of biological membranes that might be responsible for the activation of different cellular processes.
Asunto(s)
Ceramidas/metabolismo , Lípidos de la Membrana/metabolismo , Microscopía Confocal , Espectrometría de FluorescenciaRESUMEN
The plasma membrane has a highly asymmetric distribution of lipids and contains dynamic nanodomains many of which are liquid entities surrounded by a second, slightly different, liquid environment. Contributing to the dynamics is a continuous repartitioning of components between the two types of liquids and transient links between lipids and proteins, both to extracellular matrix and cytoplasmic components, that temporarily pin membrane constituents. This make plasma membrane nanodomains exceptionally challenging to study and much of what is known about membrane domains has been deduced from studies on model membranes at equilibrium. However, living cells are by definition not at equilibrium and lipids are distributed asymmetrically with inositol phospholipids, phosphatidylethanolamines and phosphatidylserines confined mostly to the inner leaflet and glyco- and sphingolipids to the outer leaflet. Moreover, each phospholipid group encompasses a wealth of species with different acyl chain combinations whose lateral distribution is heterogeneous. It is becoming increasingly clear that asymmetry and pinning play important roles in plasma membrane nanodomain formation and coupling between the two lipid monolayers. How asymmetry, pinning, and interdigitation contribute to the plasma membrane organization is only beginning to be unraveled and here we discuss their roles and interdependence.