TY - JOUR
T1 - Inhibiting lateral domain formation in lipid bilayers
T2 - Simulations of alternative steroid headgroup chemistries
AU - Perlmutter, Jason D.
AU - Sachs, Jonathan N.
PY - 2009/11/27
Y1 - 2009/11/27
N2 - (Figure Presented) Cholesterol is an essential component of lateral domain formation in lipid bilayers. Experiments using structural analogues of cholesterol have revealed that slight changes to the steroid headgroup chemistry can lead to significantly different degrees of domain formation. For example, the seemingly slight modification to 4-cholesten-3β-one changes the molecule from domain enhancing to domain inhibiting. To investigate the relationship between steroid headgroup structure and domain formation, we have performed a series of coarse-grain molecular dynamics simulations in which the hydrophobicity of the steroid headgroup is altered. We show that bilayers containing steroids with polar headgroups undergo lateral phase separation, with the steroids adopting the canonical, upright orientation. However, increasing the hydrophobicity of the steroid's headgroup dramatically changes the orientation of the molecule such that it lies at the center of the bilayer, perpendicular to the bilayer normal. As a fundamental consequence, we show that these steroids inhibit the formation of phase-separated domains in membranes.
AB - (Figure Presented) Cholesterol is an essential component of lateral domain formation in lipid bilayers. Experiments using structural analogues of cholesterol have revealed that slight changes to the steroid headgroup chemistry can lead to significantly different degrees of domain formation. For example, the seemingly slight modification to 4-cholesten-3β-one changes the molecule from domain enhancing to domain inhibiting. To investigate the relationship between steroid headgroup structure and domain formation, we have performed a series of coarse-grain molecular dynamics simulations in which the hydrophobicity of the steroid headgroup is altered. We show that bilayers containing steroids with polar headgroups undergo lateral phase separation, with the steroids adopting the canonical, upright orientation. However, increasing the hydrophobicity of the steroid's headgroup dramatically changes the orientation of the molecule such that it lies at the center of the bilayer, perpendicular to the bilayer normal. As a fundamental consequence, we show that these steroids inhibit the formation of phase-separated domains in membranes.
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U2 - 10.1021/ja9079258
DO - 10.1021/ja9079258
M3 - Article
C2 - 19860442
AN - SCOPUS:70450183660
SN - 0002-7863
VL - 131
SP - 16362
EP - 16363
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 45
ER -