From simple to complex: investigating the effects of lipid composition and phase on the membrane interactions of biomolecules using in situ atomic force microscopy

Biomembrane lipid composition and lateral heterogeneity vary significantly both spatially and temporally and have been shown to be associated with cell functions. Lipid raft-based membrane heterogeneity might be involved with cell physiological and pathological processes. Therefore, there is a great need to investigate the roles of lipid composition and lateral heterogeneity in membrane-related physiological and pathological processes. Supported lipid bilayers (SLBs) of increasing complexity are excellent membrane model systems to investigate the effects of lipid composition and phase on the membrane interactions of biomolecules. In situ AFM is a powerful tool to examine the dynamic interactions between SLBs and biomolecules on a nanoscale. Therefore, the in situ AFM measurements between SLBs of increasing complexity and biomolecules are excellent ways to investigate the effects of lipid composition and phase on the membrane-related processes. In this review, the following basic knowledge is first discussed: biomembrane lipid composition, lipid raft, lipid phase separation, SLBs, and AFM. Then the biological applications of in situ AFM to visualize the interactions between SLBs of increasing complexity and biomolecules are discussed.