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Updated: Aug 6, 2026
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Realistic Membrane Modeling Using Complex Lipid Mixtures in Simulation Studies
Published on: September 1, 2023
Coarse-grained simulation studies of Gasdermin self-assembly and pore formation
Xiuyun Jiang1, James Daniel Farrell2, Fang Jiao3
12020 X-Lab, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai, 200050, PR China; Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, PR China.
Biophysical Journal
|August 5, 2026
Summary
Gasdermins (GSDMs) form pores during pyroptosis, an immune cell death process. This study models GSDM assembly, revealing how insertion speed and protein interactions dictate pore shape and function.
Area of Science:
- Biophysics
- Molecular Biology
- Immunology
Background:
- Gasdermins (GSDMs) are key effectors of pyroptosis, a crucial inflammatory cell death pathway in immunity.
- Previous studies elucidated GSDM structure and membrane insertion but lacked understanding of pore assembly dynamics.
- Bridging atomistic and biological scales is essential for comprehending GSDM-mediated pore formation.
Purpose of the Study:
- To develop a coarse-grained model for simulating GSDM pore assembly dynamics.
- To investigate the influence of monomer insertion kinetics and protein interactions on pore structure.
- To elucidate the mechanisms governing pyroptotic pore formation relevant to biological scales.
Main Methods:
- Development of a minimal coarse-grained GSDM model.
- Extensive molecular dynamics simulations of GSDM-membrane interactions.
- Analysis of supramolecular structures (rings, slits, arcs) and their cross-sections.
Main Results:
- Simulations reproduced experimentally observed GSDM supramolecular structures.
- Pore assembly is regulated by the kinetics of monomer conformational transitions (prepore to pore state).
- Slow monomer insertion favors ring formation (promoted by protein interactions), optimizing transport.
- Fast monomer insertion favors slit formation (promoted by membrane coverage), hindering transport.
Conclusions:
- The study provides a mechanistic understanding of GSDM pore assembly dynamics.
- Findings highlight the critical role of insertion kinetics and protein interactions in determining pore morphology.
- This work offers insights for modulating pyroptosis in physiological and disease contexts.
