title: Membrane dipole potential is sensitive to cholesterol stereospecificity: implications for receptor function.
abstract: Dipole potential is the potential difference within the membrane bilayer, which originates due to the nonrandom arrangement of lipid dipoles and water molecules at the membrane interface. Cholesterol, an essential lipid in higher eukaryotic membranes, has previously been shown to increase membrane dipole potential. In this work, we explored the effect of stereoisomers of cholesterol, ent-cholesterol and epi-cholesterol, on membrane dipole potential, monitored by the dual wavelength ratiometric approach utilizing the probe di-8-ANEPPS. Our results show that cholesterol and ent-cholesterol share comparable ability in increasing membrane dipole potential. In contrast, epi-cholesterol displays a slight reduction in membrane dipole potential. Our results constitute the first report on the effect of stereoisomers of cholesterol on membrane dipole potential, and imply that an extremely subtle change in sterol structure can significantly alter the dipolar field at the membrane interface. These results assume relevance in the context of differential abilities of these stereoisomers of cholesterol in supporting the activity of the serotonin1A receptor, a representative G protein-coupled receptor. The close correlation between membrane dipole potential and receptor activity provides new insight in receptor-cholesterol interaction in terms of stereospecificity. We envision that membrane dipole potential could prove to be a sensitive indicator of lipid-protein interactions in biological membranes.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Bandari
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Hirak
authors.initials: H
authors.lastname: Chakraborty
authors.affiliation: Departments of Developmental Biology, Anesthesiology, Psychiatry and The Taylor Family Institute for Innovative Psychiatry Research, WA University in St. Louis Medical School, St. Louis, MO 63110, USA.
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Covey
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. Electronic address: amit@ccmb.res.in.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
mesh_terms: D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry; D008564:Membrane Potentials; D010743:Phospholipids / Q000737:chemistry; D011726:Pyridinium Compounds / Q000737:chemistry; D044282:Receptor, Serotonin, 5-HT1A / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: C089669:1-(3-sulfonatopropyl)-4-(beta-(2-(di-n-octylamino)-6-naphthyl)vinyl)pyridinium betaine; D008051:Lipid Bilayers; D010743:Phospholipids; D011726:Pyridinium Compounds; D053835:Unilamellar Liposomes; D044282:Receptor, Serotonin, 5-HT1A; D002784:Cholesterol
keywords: Cholesterol; Dipole potential; Ent-cholesterol; Epi-cholesterol; Serotonin(1A) receptor; di-8-ANEPPS