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A percolation phase transition controls complement protein coating of surfaces
Journal article   Peer reviewed

A percolation phase transition controls complement protein coating of surfaces

Zhicheng Wang, Sahil Kulkarni, Jia Nong, Marco Zamora, Alireza Ebrahimimojarad, Elizabeth Hood, Tea Shuvaeva, Michael Zaleski, Damodar Gullipalli, Emily Wolfe, …
Cell, v 188(15), pp 4058-4073.e25
24 Jul 2025
PMID: 40516526

Abstract

biomaterials complement complexity science host response nanomedicine Immunology Systems Biology
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. [Display omitted] •The complement protein network has a switch-like response when attacking surfaces•Complement “decides” to coat surfaces if surface protein spacing is below a threshold•Complement’s threshold decision-making arises from a percolation phase transition•Complexity science shows how complement makes discrete decisions attacking surfaces Complex systems of proteins in the body, such as the complement system, must coordinate to turn their functions on and off. This study shows that complement “decides” whether to attack a surface by distinguishing if the density of potential complement attachment points exceeds a threshold, which enables a phase transition that drives further coordination of the network.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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