The principles for the selection of the stereochemistry
of phospholipids of biological membranes remain unclear and continue
to be debated. Therefore, any new experiments on this topic may help
progress in this field. To address this question, three libraries
of constitutional isomeric glycerol-amphiphilic Janus dendrimers (JDs)
with nonsymmetric homochiral, racemic, and symmetric achiral branching
points were synthesized by an orthogonal–modular–convergent
methodology. These JDs amplify self-assembly, and therefore, monodisperse
vesicles known as dendrimersomes (DSs) with predictable dimensions
programmed by JD concentration were assembled by rapid injection of
their ethanol solution into water. DSs of homochiral JD enantiomers,
racemic, including mixtures of different enantiomers, and achiral
exhibited similar DS size-concentration dependence. However, the number
of bilayers of DSs assembled from homochiral, achiral, and racemic
JDs determined by cryo-TEM were different. Statistical analysis of
the number of bilayers and coarse-grained molecular dynamics simulations
demonstrated that homochiral JDs formed predominantly unilamellar
DSs. Symmetric achiral JDs assembled only unilamellar DSs while racemic
JDs favored multilamellar DSs. Since cell membranes are unilamellar,
these results indicate a new rationale for nonsymmetric homochiral vs racemic selection. Simultaneously, these experiments
imply that the symmetric achiral lipids forming more stable membrane,
probably had been the preferable assemblies of prebiotic cell membranes.
