Adhesion energy controls lipid binding-mediated endocytosis

Area of Science:

• Cell biology
• Biophysics
• Molecular biology

Background:

• Bacterial toxins and viruses utilize multivalent lipid binding to deform cell membranes, facilitating clathrin-independent endocytosis.
• The precise mechanistic link between membrane deformation and subsequent endocytic internalization remains incompletely understood.

Approach:

• A synthetic cellular system was engineered using lipid-anchored receptors (GPI-anchored anti-GFP nanobodies) and a multivalent globular binder (40 nm particles with 180 GFP molecules).
• The system allowed for controlled investigation of membrane deformation and endocytosis by varying receptor-ligand affinities over seven orders of magnitude.

Key Points:

• Multivalent binding of globular particles to cell surface receptors induces plasma membrane deformation and clathrin-independent endocytosis.
• A critical threshold in membrane adhesion energy is required to initiate deformation and trigger reliable endocytosis.
• Binding-induced membrane deformation by multivalent globular particles is sufficient for cellular internalization.

Conclusions:

• The study proposes a common, purely biophysical mechanism for lipid-binding mediated endocytosis of toxins and pathogens.
• Multivalent binding leading to membrane deformation is a sufficient driving force for clathrin-independent endocytosis.