Anomalous inter-membrane cholesterol transport in fluid phase phosphoserine vesicles driven by headgroup ordered to disordered entropic transition

Abstract

POPS is highly enriched in the inner leaflet of the plasma membrane. Here we present measurements of inter-membrane cholesterol transport rates in POPS vesicles. We find that the cholesterol transport kinetics are not only an order of magnitude slower than in POPC lipids at near physiological temperatures, they exhibit a surprising discontinuous Arrhenius behavior around 48 °C. Moreover, thermodynamic analysis suggests that for biologically relevant temperatures, below the discontinuity, the exchange of cholesterol is entropically dominated while it is enthalpically driven, as is the case in POPC vesicles, above that discontinuity. Using the polar fluorescent probe Laurdan we found that POPS fluid membranes retain a large degree of order in the headgroup region for temperatures below the discontinuity but undergo an order-to-disorder transition in the region coinciding with the discontinuity in the transport of cholesterol in POPS membranes providing an explanation not only for the discontinuity but for the entropic dominance at physiological temperatures.