An osmometer model for changes in the buoyant density of chromaffin granules

We present a model for the structure of isolated bovine adrenal medulla chromaffin granules derived from the dependence of granule density on the osmotic pressure of the suspension medium at 2 degrees C. The granule consists of a flexible, inelastic membrane bounding an osmotically active core. The core consists of a solution space and a separate, nonosmotic phase. Since the granule behaves like a "perfect" osmometer over a wide range of osmolarities, we conclude that (a) within these limits, the core consists of a constant amount of condensed material and a constant number of particles in solution, (b) from the constraints of the osmometer model, the osmolality inside the granule must equal the osmolality outside. Therefore the high concentrations of catecholamines (greater than 0.7 M) and ATP (greater than 0.18 M) measured biochemically cannot be dissolved in the core solution as separate molecules, but must be condensed into larger aggregates. These results are supported by electron micrographic examination of the effect of osmotic pressure changes on granule morphology.