Small-angle neutron scattering method for in situ studies of the dense cores of biological cells and vesicles: application to isolated neurosecretory vesicles

Small-angle neutron scattering was used to study the structure of the dense cores of intact neurosecretory vesicles (NSV). Contrast-variation techniques were used to minimize the scattering due to vesicle membranes and emphasize that due to the cores. By examination of a suspension of NSV membranes along with the intact NSV, residual membrane scattering was suppressed. The resultant scattering is inconsistent with model calculations which assume that the dense state of the vesicle cores is achieved by random dense packing or crystallization of small globular particles. Rather, the data suggest that the core constituents exist in a disordered state, forming aggregates with radii of gyration significantly larger than 100 Å.