Confinement effect on hydrolysis in small lipid vesicles.

In living organisms most chemical reactions take place within the confines of lipid-membrane bound compartments, while confinement within the bounds of a lipid membrane is thought to be a key step in abiogenesis. In previous work we demonstrated that confinement in the aqueous cavity of a lipid vesicle affords protection against hydrolysis, a phenomenon that we term here confinement effect (C e) and that we attributed to the interaction with the lipid membrane. Here, we show that both the size and the shape of the cavity of the vesicle modulate the C e. We link this observation to the packing of the lipid following changes in membrane curvature, and formulate a mathematical model that relates the C e to the radius of a spherical vesicle and the packing parameter of the lipids. These results suggest that the shape of the compartment where a molecule is located plays a major role in controlling the chemical reactivity of non-enzymatic reactions. Moreover, the mathematical treatment we propose offers a useful tool for the design of vesicles with predictable reaction rates of the confined molecules, e.g., drug delivery vesicles with confined prodrugs. The results also show that a crude form of signal transduction, devoid of complex biological machinery, can be achieved by any external stimuli that drastically changes the structure of the membrane, like the osmotic shocks used in the present work.