Kinetic control of liposome size by direct lipid transfer

Spontaneous lipid vesiculation and related size distribution are traditionally studied in the framework of equilibrium thermodynamics and continuum mechanics, overlooking the kinetic aspects of the process. In the scenario of liposomes consisting of different lipid molecules dispersed in the same medium - a non-equilibrium situation -, the system evolves driven by lipid monomer transfer among the different liposomes. This process encompasses time-dependent changes in liposome size and size distribution, thus predicting size and composition at a given time would entail the control of the size of liposomes by kinetic means, an asset in the framework of diagnostics and synthetic biology. We introduce a direct transfer model, based on the fact that monomers are highly reactive species and apply it to saturated phospholipid molecules differing in hydrophobic chain length. Considering a well-defined gamma-type liposome size distribution, we demonstrate a clear liposome size-composition correlation and are able to predict liposome size and size distribution at any time in the transfer process. The size-composition correlation opens up new prospects for the control of the self-assembling properties of lipids and thereby the control of the liposome size.