SGSikao Guo
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Computational biophysics

Mechanistic models of membrane-associated assembly

Connecting molecular interactions to nucleation, remodeling, and organization

Published2020 – 2024
  • NERDSS
  • Stochastic simulation
  • Kinetic modeling
  • Membranes
  • Self-assembly
  • Data integration
Abstract membrane with assembling clathrin-like lattice, a budding viral lattice, and dynamin molecules concentrating into clusters.
> 1:1
adaptor-to-clathrin threshold
~25
clathrin trimers in critical nucleus
minutes
Gag-Pol dimerization timescale

Context

The problem

Many membrane-associated assemblies are controlled by spatial geometry, stoichiometry, dimensional reduction, and kinetic timing. These effects are difficult to infer from static structures or bulk measurements alone.

The models combine molecular structures, interaction affinities, concentrations, kinetic measurements, and membrane geometry to connect microscopic rules to observable assembly behavior.

Method

How the system works

01

Clathrin nucleation

Built a structure-resolved membrane assembly model to distinguish stable and abortive lattice growth under adaptor-limited conditions.

02

HIV-1 lattice remodeling

Modeled rare Gag-Pol molecules within an incomplete immature lattice to quantify how remodeling enables protease-domain encounters.

03

Dynamin recruitment

Combined single-molecule observations with a spatiotemporal model of 3D recruitment, 2D search, lateral trapping, and nanocluster growth.

Role

My contribution

  • Designed and calibrated structure-resolved stochastic models against biochemical, structural, and time-course data.
  • Implemented simulations, parameter sweeps, first-passage-time analysis, quantitative visualization, and model validation.
  • Translated model behavior into experimentally interpretable thresholds, timescales, and mechanistic hypotheses.
  • Contributed software, formal analysis, validation, visualization, and manuscript development across interdisciplinary teams.

Result

Outcomes and scientific value

✓

Predicted that productive clathrin nucleation requires an adaptor-to-clathrin ratio above 1:1 and a critical nucleus of approximately 25 clathrin trimers.

✓

Showed that incomplete HIV-1 Gag lattices can remodel on relevant timescales and enable minute-scale Gag-Pol dimerization.

✓

Supported a model in which short-tail dynamin isoforms use activity-dependent membrane recruitment and lateral trapping to form endocytic nanoclusters.

Resources

Papers, code, and documentation

Clathrin assembly paperHIV-1 lattice paperDynamin nanocluster paperGag kinetic-control paper

Related work

Publications

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