Membrane domain-disrupting effects of 4-substitued cholesterol derivatives.
A wide range of cellular functions are thought to be regulated not only by the activity of membrane proteins, but also by the local membrane organization, including domains of specific lipid composition. Thus, molecules and drugs targeting and disrupting this lipid pattern, particularly of the plasma membrane, will not only help to investigate the role of membrane domains in cell biology, but might also be interesting candidates for therapy. We have identified three 4-substituted cholesterol derivatives that are able to induce a domain-disrupting effect in model membranes. When applied to giant unilamellar vesicles displaying liquid-ordered-liquid-disordered phase coexistence, extensive reorganization of the membrane can be observed, such as the budding of membrane tubules or changes in the geometry of the domains, to the point of complete abolition of phase separation. In this case, the resulting membranes display a fluidity intermediate between those of liquid-disordered and liquid-ordered phases.
Carrer
Dolores C
DC
Biophysics Group, BIOTEC, TU Dresden, Tatzberg 47-51, Dresden, Germany.
Schmidt
Arndt W
AW
Knölker
Hans-Joachim
HJ
Schwille
Petra
P
D000143:Acids / Q000737:chemistry; D002196:Capillaries; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004952:Esters / Q000737:chemistry; D006900:Hydroxylation; D008567:Membranes, Artificial; D015394:Molecular Structure
D000143:Acids; D004952:Esters; D008567:Membranes, Artificial; D002784:Cholesterol