Abstract

The mixing behavior of exchangeable, disulfide-based mimics of 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) and cholesterol has been examined as a function of temperature in host membranes made from DPPC and cholesterol in the liquid-disordered phase ( l d), in the liquid-ordered phase ( l o), and in the liquid-disordered/liquid-ordered coexistence region ( l d/ l o). In the l d region, lipid mixing was found to be temperature insensitive, reflecting close to ideal behavior. In contrast, a significant temperature dependence was observed in the l o phase from 45 to 60°C, when 35 or 40 mol % sterol was present. In this region, sterol-phospholipid association was characterized by Δ H o = −2.06 ± 0.14 kcal/mol of phospholipid and Δ S° = −4.48 ± 0.44 cal/K mol of phospholipid. From 60 to 65°C, the mixing of these lipids was found to be insensitive to temperature, and sterol-phospholipid association was now entropy driven; that is, Δ H o = −0.23 ± 0.38 kcal/mol of phospholipid and Δ S° = +1.68 ± 1.12 cal/K mol of phospholipid. In the liquid-disordered/liquid-ordered coexistence region, changes in lipid mixing reflect changes in the phase composition of the membrane.

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