Influence of Lipoproteins and Lipid Transfer in Copolymer Micelle Instability

Micelle stability in complex biologic fluids is relatively uncharacterized. Much of the work in the field has focused on the influence of proteins, however the influence of complex lipid particles such as lipoproteins is relatively unexplored. The influence of complex biologic fluids and individual human lipoprotein classes on micelle stability was explored utilizing Forster resonance energy transfer and density ultracentrifugation. Cerebrospinal, ascites, and pleural fluid were identified as relatively stable fluids for micelles and appeared to correlate with lipoprotein content. The influence of individual lipoproteins revealed high density lipoprotein as a significant destabilizer of two copolymer micelles. The influence of lipid transfer and potential mixed micelle formation was also explored by MS-ESI/LC-MS/MS as well as SANS, which revealed selective enrichment of several lipid classes and general depletion among others. The potential for lysolipid mixed micelle formation influence on human monocyte derived macrophages was also explored utilizing a known pro-resolving lipid mediator.