Regulating the Size and Stabilization of Lipid Raft-like Domains and Using Calcium Ions as Their Probe

Abstract

We apply a means to probe, stabilize, and control the size of lipid raft-like domains in vitro. In biomembranes the size of lipid rafts is ca. 10-30 nm. In vitro, mixing saturated and unsaturated lipids results in microdomains, which are unstable and coalesce. This inconsistency is puzzling. It has been hypothesized that biological line-active surfactants reduce the line tension between saturated and unsaturated lipids and stabilize small domains in vivo. Using solution X-ray scattering, we studied the structure of binary and ternary lipid mixtures in the presence of calcium ions. Three lipids were used: saturated, unsaturated, and a hybrid (1-saturated-2-unsaturated) lipid that is predominant in the phospholipids of cellular membranes. Only membranes composed of the saturated lipid can adsorb calcium ions, become charged, and therefore considerably swell. The selective calcium affinity was used to show that binary mixtures, containing the saturated lipid, phase separated into large-scale domains. Our data suggests that by introducing the hybrid lipid to a mixture of the saturated and unsaturated lipids, the size of the domains decreased with the concentration of the hybrid lipid, until the three lipids could completely mix. We attribute this behavior to the tendency of the hybrid lipid to act as a line-active cosurfactant that can easily reside at the interface between the saturated and the unsaturated lipids and reduce the line tension between them. These findings are consistent with a recent theory and provide insight into the self-organization of lipid rafts, their stabilization, and size regulation in biomembranes.

Physical mechanisms of micro- and nanodomain formation in multicomponent lipid membranes

“…In particular, they sug-gested that hybrid lipids with one saturated and one unsaturated tail may serve as linactants that accumulate at ld-lo boundaries and reduce the line tensions. This hypothesis is consistent with a number of experimental findings [63,64,132]. Here we specifically discuss the work on fourcomponent mixtures by Feigenson and coworkers [63,64] which lead to the structures shown in Fig.…”

Decreases in Phospholipids Containing Adrenic and Arachidonic Acids Occur in the Human Hippocampus over the Adult Lifespan

“…The role of this particular molecular phospholipid is largely unknown; however, its high abundance could suggest a structural or scaffolding role in cellular membranes. Some evidence points to a role for PtdCho 16:0_18:1 in modulating membrane fluidity [30,31], as well as participating in the formation of lipid raft domains [32]. Our previous study of the prefrontal cortex also found age-related changes for mitochondrial PtdCho 16:0_18:1 [22].…”

D+: Software for High-Resolution Hierarchical Modeling of Solution X-Ray Scattering from Complex Structures

“…The challenge of structural biophysics is to determine the high-resolution structure of large self-assembled complexes, made of many subunits, in their biologically relevant solution conditions. Solution small-and wide-angle X-ray scattering (SAXS/WAXS) methods are one of the important labelfree and highly sensitive bulk methods for investigating the structure and interactions between complex molecular constructs (Rädler et al, 1997;Koltover et al, 1998;Schilt et al, 2016;Dvir et al, 2014;Dvir et al, 2013;Chung et al, 2015;Chung et al, 2016;Lotan et al, 2016;Ojeda-Lopez et al, 2014;Moshe et al, 2013;Saper et al, 2012;Steiner et al, 2012;Szekely et al, 2011a;Szekely et al, 2011b;Choi et al, 2009;Choi et al, 2016;Wong et al, 2000;Deek et al, 2013;Beck et al, 2010;Kornreich et al, 2016;Shaharabani et al, 2016;Ginsburg et al, 2017;Asor et al, 2017;Fink et al, 2017a). With modern synchrotron facilities the temporal and spatial resolution of these methods has been greatly improved Kler et al, 2012).…”