Building synthetic cell-cell synapses using engineered scaffold protein condensates

Engineered modular scaffold proteins with PDZ domains and IDRs show switch-like, thresholded condensation at cell-cell interfaces, selectively forming co-condensates only with the proper partner cell.

• Why it matters: Natural synaptic assemblies may rely on multivalent scaffolds that act as thresholding devices, but it is unclear whether receptor-density changes can trigger all-or-none assembly at correct interfaces.
• What they did: Coarse-grained simulations predicted a sharp condensation threshold, and modular PDZ–IDR scaffold proteins were designed and tested across parameter space set by valency, receptor binding affinity, and IDR-driven condensation.
• The result: Orthogonal receptor–scaffold pairs let one receiver cell form multiple distinct interfaces with different partner cells, and the assemblies recruit client proteins to enhance signaling, orient division, or sculpt synaptic morphologies.