Toward a mechanism of myoblast fusion

Myoblasts derived from chick pectoral muscle explants and grown in vitro in low calcium medium are harvested with EDTA. These cells, when agitated in suspension, show a calcium mediated, reversible aggregation which is relevant to myoblast function. With time, progressively harsher methods are required to disrupt the aggregates until, finally, dispersion resistant aggregates and multinucleate cells appear. From these kinetic data we conclude that myoblast fusion results from a sequence of stages including recognition, adhesion, membrane union, and further morphologic changes. Various agents and manipulations, known to inhibit myotube formation, affect these stages differently. Our observations are compatible with protein mediated recognition and adhesion-stages, and with a role for the cytoskeleton, Ca2+, and fluid membrane lipids at a stage at, or just prior to, membrane union. One model consistent with our observations is an adhesive step, possibly via a gap junction-like structure, followed by directed movement of protein, which results in closely apposed or exposed regions of lipid bilayer, which then fuse.