A percolation phase transition controls complement protein coating of surfaces

Area of Science:

• Biomaterials Science
• Immunology
• Systems Biology

Background:

• Materials entering the body trigger complex protein interactions, primarily involving the complement system.
• The complement system, comprising ~40 blood proteins, initiates inflammation upon binding to microbes, nanoparticles, and medical devices.
• Understanding the precise mechanisms governing complement system activation by materials is crucial for biomedical applications.

Purpose of the Study:

• To investigate the relationship between material properties and complement system activation.
• To identify the critical material parameters that dictate the "decision" of the complement system to attack.
• To elucidate the underlying network dynamics of complement activation.

Main Methods:

• Experimental variation of a key material parameter: surface density of complement attachment points.
• Observation of complement activation across diverse scales, from nanoparticles to macroscale pathologies.
• Development of computational models simulating minimal complement subnetworks.

Main Results:

• A sharp activation threshold for the complement system was identified, directly correlated with material surface density.
• This critical transition phenomenon was observed consistently across various engineered and biological materials.
• Computational models revealed percolation-type critical transitions in the complement response, driven by minimal subnetworks.

Conclusions:

• The "decision" of the complement system to attack a material is governed by a critical switch mechanism.
• Material surface properties, specifically attachment point density, dictate complement activation thresholds.
• The findings offer fundamental insights into host-material interactions and immune responses.