Molecular Crowding and Diffusion-Capture in Synapses

Cell membranes often contain domains with important physiological functions. A typical example are neuronal synapses, whose capacity to capture receptors for neurotransmitters is central to neuronal functions. Receptors diffuse in the membrane until they are stabilized by interactions with stable elements, the scaffold. Single particle tracking experiments demonstrated that these interactions are rather weak and that lateral diffusion is strongly impaired in the post-synaptic membrane due to molecular crowding. We investigated how the distribution of scaffolding molecules and molecular crowding affect the capture of receptors. In particle-based Monte Carlo simulations, based on experimental data of molecular diffusion and organization, crowding enhanced the receptor-scaffold interaction but reduced the capture of new molecules. The distribution of scaffolding sites in several clusters reduced crowding and fostered the exchange of molecules accelerating synaptic plasticity. Synapses could switch between two regimes, becoming more stable or more plastic depending on the internal distribution of molecules. [Display omitted] •The good: molecular crowding enhances the interaction receptors-scaffold•The bad: the exchange of molecules with extrasynaptic areas is reduced by crowding•Molecular crowding helps synapses to be stable•Nanoclusters of scaffold sites reduce crowding effects and favor synaptic plasticity Neuroscience; Molecular Neuroscience; In Silico Biology