Molecular assemblies of highly PEG-ylated phospholipids are important in many biomedical applications. We have studied sterically stabilized micelles (SSMs) of self-assembled DSPEPEG2000 in pure water and isotonic HEPES-buffered saline solution. The observed SSM sizes of 215 nm largely depend on the solvent and the lipid concentration used. The critical micelle concentration of DSPEPEG(2000) is similar to 10 times higher in water than in buffer, and the viscosity of the dispersion dramatically increases with the lipid concentration. To explain the experimentally observed results, we performed atomistic molecular dynamics simulations of solvated SSMs. Our modeling revealed that the observed assemblies have very different aggregation numbers (N-agg approximate to 90 in saline solution and N-agg < 8 in water) because of very different screening of their charged PO4 groups. We also demonstrate that the micelle cores can inflate and their coronas can fluctuate strongly, thus allowing storage and delivery of molecules with different chemistries.