Diffusion-driven self-assembly of emerin nanodomains at the nuclear envelope

TL;DR

This study combines theory and experiments to model how emerin proteins self-assemble into nanodomains at the nuclear envelope, revealing how mechanical stress and mutations affect their organization and providing insights into Emery-Dreifuss muscular dystrophy.

Contribution

A reaction-diffusion model is developed that accurately explains emerin nanodomain formation and predicts effects of mutations and mechanical forces, advancing understanding of nuclear membrane organization.

Findings

Model matches experimental nanodomain sizes and occupancy.

Mutations and forces alter emerin diffusion and organization.

Predicts diffusion coefficients from nanodomain properties.

Abstract

Emerin, a nuclear membrane protein with important biological roles in mechanotransduction and nuclear shape adaptation, self-assembles into nanometer-size domains at the inner nuclear membrane. The size and emerin occupancy of these nanodomains change with applied mechanical stress as well as under emerin mutations associated with Emery-Dreifuss muscular dystrophy (EDMD). Through a combination of theory and experiment we show here that a simple reaction-diffusion model explains the self-assembly of emerin nanodomains. Our model yields quantitative agreement with experimental observations on the size and occupancy of emerin nanodomains for wild-type emerin and EDMD-associated mutations of emerin, with and without applied forces, and allows successful prediction of emerin diffusion coefficients from observations on the overall properties of emerin nanodomains. Our results provide a physical understanding of EDMD-associated defects in emerin organization in terms of changes in key reaction and diffusion properties of emerin and its nuclear binding partners.