Nambiar, N. | Search bioRxiv

bioRxiv2026

The reticulon homology domain of Pex30 generates membrane curvature at ER subdomains for lipid droplet biogenesis

Lipid droplets (LDs) are dynamic organelles that store neutral lipids and form in the endoplasmic reticulum (ER) membrane. Formation of new LDs is a controlled process and requires proteins with specific functions to form and grow from the ER membrane without any defect. In vitro studies have suggested a role for membrane curvature in LD emergence from the ER. Here, we use the membrane-shaping protein Pex30 to investigate the impact of ER membrane curvature on LD biogenesis and morphology. We modified the reticulon homology domain (RHD) of Pex30, which is responsible for tubulating the ER membrane, by extending the short hairpin transmembrane domains (TMD). The Pex30 (TMD) mutants cannot tubulate the ER membrane and generate less local membrane curvature that WT Pex30. Additionally, these mutants are unable to restore delayed LD biogenesis observed in cells devoid of Pex30. Our results indicate that Pex30 RHD generates local membrane curvature at ER subdomains that drives formation of new LDs.

cell biology↗

bioRxiv2023

Particle deformability enables control of interactions between membrane-anchored nanoparticles

Nanoparticles adsorbed on a membrane can induce deformations of the membrane that give rise to effective interactions between the particles. Previous studies have focused primarily on rigid nanoparticles with fixed shapes. However, DNA origami technology has enabled the creation of deformable nanostructures with controllable shapes and mechanical properties, presenting new opportunities to modulate interactions between particles adsorbed on deformable surfaces. Here we use coarse-grained molecular dynamics simulations to investigate deformable, hinge-like nanostructures anchored to lipid membranes via cholesterol anchors. We characterize deformations of the particles and membrane as a function of the hinge stiffness. Flexible particles adopt open configurations to conform to a flat membrane, whereas stiffer particles induce deformations of the membrane. We further show that particles spontaneously aggregate and that cooperative effects lead to changes in their shape when they are close together. Using umbrella sampling methods, we quantify the effective interaction between two particles and show that stiffer hinge-like particles experience stronger and longer-ranged attraction. Our results demonstrate that interactions between de-formable, membrane-anchored nanoparticles can be controlled by modifying mechanical properties of the particles, suggesting new ways to modulate the self-assembly of particles on deformable surfaces.

biophysics↗