The association of lipid molecules into spherical vesicles in solution
as a result of nonspecific intermolecular forces constitutes a primar
y self-assembly process. Such vesicles can undergo a secondary self-as
sembly into higher order structures in a controlled and reversible man
ner by means of site-specific ligand-receptor (biotin-streptavidin) co
upling. Cryoelectron microscopy shows these structures to be composed
of tethered, rather than adhering, vesicles in their original, unstres
sed state. In contrast, vesicles aggregated by nonspecific, such as va
n der Waals, forces are deformed and stressed, producing unstable stru
ctures. Vesicle association by site-specific binding provides a practi
cal mechanism for the production of stable, yet controllable, microstr
uctured biomaterials.