Evidence map›Paper›PMID 40516526›Full record

ArticleCell2025

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 and 11 more

Abstract read
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

Zhicheng WangPulmonary, Allergy, and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sahil KulkarniDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jia NongDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Marco ZamoraPulmonary, Allergy, and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Alireza EbrahimimojaradCenter for Computational and Integrative Biology, Rutgers University-Camden, Camden, NJ 08103, USA.
Elizabeth HoodDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Tea ShuvaevaDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael ZaleskiDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Damodar GullipalliDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Emily WolfeSchool of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, USA.
Carolann EspyDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Evguenia ArguiriDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jichuan WuPulmonary, Allergy, and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yufei WangPulmonary, Allergy, and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Oscar A Marcos-ContrerasDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Wenchao SongDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Vladimir R MuzykantovDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jinglin FuCenter for Computational and Integrative Biology, Rutgers University-Camden, Camden, NJ 08103, USA.
Ravi RadhakrishnanDepartment of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Institute for Computational Science, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: rradhak@seas.upenn.edu.
Jacob W MyersonDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: myerson@pennmedicine.upenn.edu.
Jacob S BrennerPulmonary, 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.

Funding

Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4M
A physical sciences approach to investigate the role of exosomes in metastatic progressionU01CA250044 · NCI · UNIVERSITY OF PENNSYLVANIA · PI GUO, WEI, RADHAKRISHNAN, RAVI · 2021 to 2025
$3.9M
Multiscale Modeling to Optimize Inhibition of Oncogenic ERK Pathway SignalingR01CA244660 · NCI · YALE UNIVERSITY · PI HLAVACEK, WILLIAM S, KHOLODENKO, BORIS N · 2020 to 2024
$3.4M
Regulation of cell, tissue, and nucleus function by mechanical properties of biopolymer networksR35GM136259 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Paul A Janmey · 2020 to 2026
$3.2M
Dual drug delivery to lung/blood interface in respiratory infections.R01HL157189 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MUZYKANTOV, VLADIMIR R · 2021 to 2024
$2.9M
Controlling complement to unleash nanomedicine for acute critical illnessesR01HL160694 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB, MUZYKANTOV, VLADIMIR R · 2022 to 2025
$2.7M
Nanomedicine for ARDS: A new paradigm to target drugs to multiple cell types within alveolar capillariesR01HL153510 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BRENNER, JACOB · 2020 to 2024
$2.0M
Targeting the gatekeepers: Bolstering blood-brain barrier function using targeted nanomedicine in acute ischemic strokeR01NS131279 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Oscar A. Marcos-Contreras · 2024 to 2026
$1.2M
NCATS NIH HHS UL1 TR001878NCI NIH HHS R01 CA244660NCI NIH HHS U01 CA250044NHLBI NIH HHS R01 HL153510NHLBI NIH HHS R01 HL157189NHLBI NIH HHS R01 HL160694NIGMS NIH HHS R35 GM136259NINDS NIH HHS R01 NS131279
6 · The paper itself

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.

Indexed as

Complement System ProteinsAnimalsComplement ActivationHumansNanoparticlesPhase TransitionProtein BindingSurface PropertiesComplement System Proteinsbiomaterialscomplementcomplexity sciencehost responseimmunologynanomedicinesystems biology

Identifiers

PMID40516526
PMCPMC12243617

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.