Isolating pure postsynaptic densities in vitro
An old study by Cohen et al looked at the structure and protein composition of postsynaptic densities (PSDs) in neurons of the cerebral cortex. They isolated the PSDs by breaking apart the cells (homogenizing them) and then centrifuging to separate other organelles from the nerve terminals. Here is a electron micrograph of part of the synaptosome they isolated, with arrows shown on the postsynaptic densities:
The authors estimate that ~ 2% of the proteins in the postsynaptic density fraction are due to membrane contamination. They speculate that the majority of this contamination occurred during homogenization. So, the native morphological appearance of PSDs is largely maintained. This bodes well for other extraction and preservation techniques.
Reference
RS Cohen, F Blomberg, K Berzins, and P Siekevitz. The structure of postsynaptic densities isolated from dog cerebral cortex: I. overall morphology and protein composition. J Cell Biol 1977 74:181-203. Published July 1, 1977, doi:10.1083/jcb.74.1.181