FIGURE 1.

Plasma membrane-associated expression results in high local TNFR concentrations in the TNFR-accessible shell (L_edR) around the cell resulting in dimer formation in the absence of ligand despite low auto-affinity (KD_P). Ligand trimers preferentially bind with higher affinity to dimeric (KD_RD) than to monomeric receptor (KD_RM) species. Liganded TNFR dimers are more stable than ligand-free TNFR dimers and are thus removed from the equilibrium with the monomers. Le Chatelier’s principle promotes then the net formation of new ligand-free receptor dimers. R_C, radius of the cell; V_RS, volume of the receptor accessible shell.