Lipid Microdomains in Synapse Formation

Membrane lipid rafts (i.e., cholesterol/sphingolipids domains) exhibit functional roles in both healthy and pathological states of the nervous system. However, due to their highly dynamic nature, it remains a challenge to characterize the fundamental aspects of lipid rafts that are important for specific neuronal processes. An experimental approach is presented here that allows for the interfacing of living neurons with an experimentally accessible model membrane where lipid order in cellular rafts can be reproducibly mimicked. It is demonstrated that coexisting lipid microdomains in model membranes can regulate axonal guidance and establish stable presynaptic contacts when interfaced with neurons in vitro. Experimental evidence is provided where specific functional groups and lateral organizations are favored by neurons in establishing synaptic connections. The model membrane platform presented in this work provides an accessible and direct means to investigate how lipid rafts regulate synapse formation. This experimental platform can similarly be extended to explore a variety of other cellular events where lipid lateral organization is believed to be important.