A percolation phase transition controls complement protein coating of surfaces.

Abstract

When a material enters the body, it is immediately attacked by hundreds of proteins, organized into complex networks of binding interactions and reactions. How do such complex systems interact with a material, "deciding" whether to attack? We focus on the complement system of ∼40 blood proteins that bind microbes, nanoparticles, and medical devices, initiating inflammation. We show a sharp threshold for complement activation upon varying a fundamental material parameter, the surface density of potential complement attachment points. This sharp threshold manifests at scales spanning single nanoparticles to macroscale pathologies, shown here for diverse engineered and living materials. Computational models show these behaviors arise from a minimal subnetwork of complement, manifesting percolation-type critical transitions in the complement response. This criticality switch explains the "decision" of a complex signaling network to interact with a material.
Copyright © 2025. Published by Elsevier Inc.

Authors

Zhicheng Wang, Sahil Kulkarni, Jia Nong, Marco Zamora, Alireza Ebrahimimojarad, Elizabeth Hood, Tea Shuvaeva, Michael Zaleski, Damodar Gullipalli, Emily Wolfe, Carolann Espy, Evguenia Arguiri, Jichuan Wu, Yufei Wang, Oscar A Marcos-Contreras, Wenchao Song, Vladimir R Muzykantov, Jinglin Fu, Ravi Radhakrishnan, Jacob W Myerson, Jacob S Brenner

Pulmonary, Allergy, and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: jacob.brenner@pennmedicine.upenn.edu.