Fig. 8: Membrane curvature and CD45 exclusion contribute to TCR triggering.
From: The interplay between membrane topology and mechanical forces in regulating T cell receptor activity
Micropatterned surfaces were prepared in 2D with gold nanoparticles (NPs) at the same level as an SLB (a) or in 3D with gold NPs elevated 10 nm on SiO2 pillars above the SLB (b). Anti-CD3 Fab was linked to NPs and ICAM-l molecules were present on the SLB for adhesion. Large membrane curvature is generated at engaged TCR clusters in the 2D system to accommodate large ICAM-1/LFA-1 complexes (a) whereas elevation of anti-CD3 Fab in the 3D system generates less membrane curvature for a given ligand spacing (b). However, when the distance between NP pillars is reduced to 40 nm TCR signaling is restored (b, left). This might be explained by a high degree of membrane curvature when ICAM-1/LFA-1 interactions are interspersed with the closely spaced pMHC/TCR (b, left). While ICAM-1 didn’t accumulate in 3D TCR clusters with 40 nm spacing, a relatively small number of interspersed ICAM-1/LFA-1 interactions would be sufficient to enforce curvature; further work is required to test for high curvature in the 3D 40 nm clusters.
