Synaptic differentiation can be evoked by polymer microbeads that mimic localized pericellular proteolysis by removing proteins from adjacent surfaces

Abstract

Synaptic differentiation is normally “induced” by regulatory signals that are exchanged only at close contacts between neurites and their predetermined target cells. These signals can, however, be mimicked by contact of either cell with some kinds of polymer microbeads. To find what bead action is responsible for this mimicry, we compared the effects of active and inert microbeads on Xenopus muscle cells developing in culture and on glass-adsorbed films of laminin or fibronectin. Our results show that inductive bioactivity is a property of native polystyrene microbeads that (a) is not dependent merely on bead-muscle adhesion, (b) can be eliminated simply by exposing the beads to inert serum proteins, and (c) correlates closely with the ability of some beads to desorb proteins from adjacent surfaces. Quasi-synaptic differentiation of the muscle surface thus seems to be triggered by the focal removal of peripheral cell surface components, rather than by direct bead interactions with membrane receptors or ion channels or their gradual acquisition of endogenous regulatory substances. Since nerve-muscle interaction also causes an elimination of extracellular matrix proteins from the muscle surface, very early in synapse development, we consider the possibility that the extracellular degradation of peripheral surface components contributes to the transmission of inductive positional signals during synaptogenesis.