The effect of increasing solute size on phosphatidylcholine phase behaviour at a range of hydrations was investigated using differential scanning calorimetry. Dehydration of phospholipid membranes gives rise to a compressive stress within the bilayers that promotes fluid-to-gel phase transitions. According to the Hydration Forces Explanation, sugars in the intermembrane space minimize the compressive stress and limit increases in the fluid-gel transition temperature, Tm, by acting as osmotic and volumetric spacers that hinder the close approach of membranes. However, the sugars must remain between the bilayers in order to limit the rise in Tm. Large polymers are excluded from the interlamellar space during dehydration and do not limit the dehydration-induced rise in Tm. In this study, we used maltodextrins with a range of molecular weights to investigate the size-exclusion limit for polymers between phosphatidylcholine bilayers. Solutes with sizes ranging from glucose to dextran 1000 limited the rise in lipid Tm during dehydration, suggesting that they remain between dehydrated bilayers. At the lowest hydrations the solutions vitrified, and Tm was further depressed to about 20 °C below the transition temperature for the lipid in excess water, To. The depression of Tm below To occurs when the interlamellar solution vitrifies between fluid phase bilayers. The larger maltodextrins, dextran 5000 and 12,000, had little effect on the Tm of the PCs at any hydration, nor did vitrification of these larger polymers affect the lipid phase behaviour. This suggests that the larger maltodextrins are excluded from the interlamellar region during dehydration
