Abstract

Membrane fusion is a fundamental process in cell biology, essential for organelle communication and maintenance of cellular homeostasis. This study investigates the biophysical mechanism underlying the fusion of peroxisome and lipid droplet (LD) membranes, a critical interaction for lipid metabolism and organelle function. While classical membrane fusion theory focuses on bilayer-bilayer interactions, the fusion of a peroxisome's bilayer membrane with an LD's monolayer membrane presents a unique structural challenge. Using a continuum model based on the classical theory of fusion, we analyzed the energetic landscape of this monolayer-bilayer fusion event. The objective was to characterize the intermediate structure, termed the **π-shaped structure**, formed as a result of the LD monolayer and peroxisome bilayer merging. Our analysis demonstrates that the π-shaped structure is analogous to the hemifusion diaphragm in classical bilayer fusion, representing a key intermediate state. Crucially, we show that the **expansion** of this π-shaped structure becomes more energetically favorable with a decrease in the spontaneous curvature of the membrane monolayers. This finding suggests that the physical properties of the lipids, specifically their tendency to form curved structures, are a primary determinant of the fusion efficiency between these two organelles. The results provide a theoretical framework that is consistent with experimental observations of LD-peroxisome fusion, offering significant insights into the regulation of inter-organelle lipid transfer and the broader biophysics of membrane remodeling.