Capillary physics links HIV capsid geometry to nuclear pore translocation
7 affiliations
- 1Department of Physics, Durham University, Durham DH1 3LE, United Kingdom
- 2Department of Applied Mathematics, School of Mathematics and Statistics, University of New South Wales, Sydney, NSW 2052, Australia
- 3School of Physics, University of New South Wales, Sydney, NSW 2052, Australia
- 4Australian Research Council Centre of Excellence for the Mathematical Analysis of Cellular Systems, University of New South Wales Node, Sydney, NSW 2052, Australia
- 5Department of Biotechnology and Biomedicine, DTU Bioengineering, Danmarks Tekniske Universitet, Kgs. Lyngby 2800, Denmark
- 6School of Biomedical Sciences, European Molecular Biology Laboratory Australia Node in Single Molecule Science, University of New South Wales, Sydney, NSW 2052, Australia
- 7School of Engineering, Institute for Multiscale Thermofluids, University of Edinburgh, Edinburgh EH9 3FB, United Kingdom
Abstract
The protective capsid encasing the genetic material of HIV can traverse the nuclear pore complex (NPC) intact, despite being far larger than conventional passive cargo. This is attributed to the properties of the capsid surface, which promote partitioning into cohesive assemblies of the disordered proteins that form the NPC’s permeability barrier: phenylalanine-glycine nucleoporins (FG-Nups). The implication, at the mesoscale, is that capsid–NPC interactions are characterized by the interfacial physics of wetting and capillarity. To capture this, we develop a minimal theory that reduces to an interplay between capsid geometry, effective cytoplasmic and nucleoplasmic contact angles, and a ratio of interfacial tensions. By combining analytical calculations, sharp- and diffuse-interface numerics, we make several predictions: A geometry-dependent trade-off between penetration depth and the wetting transition; asymmetric capillary forces that generate torques and lead to metastable “stalled” states that are tilted; a topological classification of the possible mechanisms underlying the largest energetic barrier; and spontaneous symmetry breaking of displaced FG-Nups. These behaviors connect capsid shape and orientation to the topology and symmetry of FG-Nup displacement, and to the molecular compositions on each side of the pore. They are consistent with published cryoelectron tomography orientations, which provide an initial estimate of the cytoplasmic contact angle. Crucially, our results identify a capillary advantage for the HIV capsid’s characteristic broken-symmetry geometry.
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BibTeX
@article{brown2026capillary,
title = {{Capillary physics links HIV capsid geometry to nuclear pore translocation}},
author = {Alexander W. Brown and Sami C. Al-Izzi and Jack L. Parker and Sophie Hertel and David A. Jacques and Halim Kusumaatmaja and Richard G. Morris},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2605059123},
url = {https://doi.org/10.1073/pnas.2605059123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Capillary physics links HIV capsid geometry to nuclear pore translocation
AU - Alexander W. Brown
AU - Sami C. Al-Izzi
AU - Jack L. Parker
AU - Sophie Hertel
AU - David A. Jacques
AU - Halim Kusumaatmaja
AU - Richard G. Morris
PY - 2026
DA - 2026/10/23
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2605059123
UR - https://doi.org/10.1073/pnas.2605059123
AB - The protective capsid encasing the genetic material of HIV can traverse the nuclear pore complex (NPC) intact, despite being far larger than conventional passive cargo. This is attributed to the properties of the capsid surface, which promote partitioning into cohesive assemblies of the disordered proteins that form the NPC’s permeability barrier: phenylalanine-glycine nucleoporins (FG-Nups). The implication, at the mesoscale, is that capsid–NPC interactions are characterized by the interfacial physics of wetting and capillarity. To capture this, we develop a minimal theory that reduces to an interplay between capsid geometry, effective cytoplasmic and nucleoplasmic contact angles, and a ratio of interfacial tensions. By combining analytical calculations, sharp- and diffuse-interface numerics, we make several predictions: A geometry-dependent trade-off between penetration depth and the wetting transition; asymmetric capillary forces that generate torques and lead to metastable “stalled” states that are tilted; a topological classification of the possible mechanisms underlying the largest energetic barrier; and spontaneous symmetry breaking of displaced FG-Nups. These behaviors connect capsid shape and orientation to the topology and symmetry of FG-Nup displacement, and to the molecular compositions on each side of the pore. They are consistent with published cryoelectron tomography orientations, which provide an initial estimate of the cytoplasmic contact angle. Crucially, our results identify a capillary advantage for the HIV capsid’s characteristic broken-symmetry geometry.
SN - 0027-8424
SN - 1091-6490
ER -