The Cytoskeleton—An Important Regulator of Membrane Protein Condensation

In our research, we use both Monte Carlo simulations and mean field theory to investigate how the cytoskeleton affects the condensation of integral membrane proteins during cell adhesion and what functional consequences arise from this process.

On the cover of the June 2 issue of Biophysical Journal, we show a cartoon of the adhesion interface between two cells. The upper and lower flexible membranes are connected via intercellular receptor-ligand complexes. The dynamic cytoskeletal network (golden yellow) lies underneath the cell membranes and is tightly attached to them through linker proteins (red). Branching of the cytoskeletal network can exert protrusive forces on the cell membrane, driving membrane deformation and protrusion. The transmembrane receptors (purple) and ligands (light blue) can interact with the cytoskeleton while experiencing spatial confinement imposed by the cytoskeletal network. The protein distribution and receptor-ligand interaction are regulated by the cytoskeleton.

The research shown in this article indicates that the steric hindrance imposed on adhesion proteins and the protrusive forces exerted on the cell membrane by cytoskeletal networks can cooperatively drive protein condensation and facilitate phase separation during cell adhesion. The intercellular receptor-ligand interaction can be either enhanced or suppressed, depending on the interplay between cytoskeleton-protein and cytoskeleton-membrane interactions.

—— Long Li, Junai Li, Zhenyuan Li, Meiying Luo, Ruotian Du, Yingfeng Shao, Yan Li, Jinglei Hu, and Fan Song