Localized osmotic swelling and cell fusion in erythrocytes: possible implications for exocytosis

Factors that govern the experimentally induced fusion of erythrocytes with one another may generally be relevant to whether or not osmotic forces drive membrane fusion in exocytosis because, under appropriate conditions, osmotic swelling can drive the fusion of erythrocytes. It is now reported that these cells fuse when they are subjected to osmotic swelling caused by exposure to small permeant molecules. The behaviour of erythrocytes in fusion induced by treatment with a concentrated solution of high molecular weight poly(ethylene glycol) (PEG) is also of specific interest in relation to exocytosis because the haemoglobin of erythrocytes that are dehydrated by concentrated solutions of the polymer may be regarded as a model for the tightly packed, dehydrated contents of the granules in secretory cells. We have observed that, under certain conditions of rehydration, the swelling of aqueous microdroplets between the dehydrated haemoglobin and the plasma membrane is closely associated with the fusion of partially rehydrated but still shrunken, PEG-treated erythrocytes. It is therefore apparent that osmotic forces, acting locally at the sites of aqueous microdroplets, can drive the fusion of membranes that encapsulate a dehydrated, concentrated protein, even though gross osmotic swelling at the level of the light microscope is absent. This finding is consistent with the possibility that osmotic swelling may play a role in exocytotic membrane fusion if it is restricted to a small zone immediately under the granule membrane.