Imaging the selective binding of synapsin to anionic membrane domains

Area of Science:

• Neuroscience
• Biophysics
• Materials Science

Background:

• Synapsins are crucial proteins regulating neurotransmitter release by maintaining synaptic vesicle pools.
• Understanding synapsin interactions with lipid bilayers is key to elucidating synaptic vesicle dynamics.
• Phase-separated lipid bilayers provide a model system to study protein-lipid interactions.

Purpose of the Study:

• To investigate the interaction of synapsin I with negatively charged lipid domains.
• To explore the binding mechanisms of synapsin I on model cell membranes.
• To assess the utility of synapsin I in visualizing lipid domains.

Main Methods:

• Preparation of phase-separated supported lipid bilayers from phosphatidylcholines (PCs) and phosphatidylserines (PSs).
• Utilizing Atomic Force Microscopy (AFM) to probe protein-lipid interactions at the nanoscale.
• Employing synapsin-coated AFM tips for enhanced visualization.

Main Results:

• Synapsin I exhibits both electrostatic binding to anionic PS-rich domains and nonspecific binding to PC phases.
• AFM imaging reveals synapsin I binding patterns correlate with charged lipid domain distribution.
• Synapsin I binding and AFM tip functionalization can visualize lipid domains undetectable by topography alone.

Conclusions:

• Synapsin I preferentially interacts with negatively charged lipid domains in model membranes.
• AFM combined with synapsin I offers a novel method for detecting and characterizing charged lipid domains.
• This approach advances our understanding of synaptic protein interactions and membrane organization.