Capillarity Reveals the Role of Capsid Geometry in HIV Nuclear Translocation

TL;DR

This paper investigates how the geometry of HIV capsids influences their ability to translocate into the nucleus, using capillarity theory and simulations to reveal physical mechanisms behind this process.

Contribution

It introduces a capillarity-based framework to explain the role of capsid shape in HIV nuclear entry, combining analytical and numerical methods.

Findings

Capsid reorientation due to asymmetric capillary forces.

Confinement limits capsid penetration depth.

Capsid translocation mechanics depend on topology and interfacial area.

Abstract

The protective capsid encasing the genetic material of Human Immunodeficiency Virus (HIV) has been shown to traverse the nuclear pore complex (NPC) intact, despite exceeding the passive diffusion threshold by over three orders of magnitude. This remarkable feat is attributed to the properties of the capsid surface, which confer solubility within the NPC's phase-separated, condensate-like barrier. In this context, we apply the classical framework of wetting and capillarity -- integrating analytical methods with sharp- and diffuse-interface numerical simulations -- to elucidate the physical underpinnings of HIV nuclear entry. Our analysis captures several key phenomena: the reorientation of incoming capsids due to torques arising from asymmetric capillary forces; the role of confinement in limiting capsid penetration depths; the classification of translocation mechanics according to changes in topology and interfacial area; and the influence of (spontaneous) rotational symmetry-breaking on energetics. These effects are all shown to depend critically on capsid geometry, arguing for a physical basis for HIV's characteristic capsid shape.