A theoretical model of lipid raft-mediated endocytosis

Abstract

Lipid rafts, functioning as specialized microdomains in the plasma membrane, are critically involved in facilitating endocytosis. While substantial evidence underscores the importance of lipid rafts and their interplay with the actin cytoskeleton in driving membrane invagination, the mechanical principles governing their coordinated action remain incompletely understood. To address this, we develop a theoretical model of lipid raft-mediated endocytosis based on Helfrich elastic membrane theory through introducing active cytoskeletal forces exerted on the lipid raft. This model enables a systematic investigation into how raft domain size and active cytoskeletal forces collectively regulate membrane deformation and endocytic efficiency. Our results show that raft size primarily governs the extent of membrane invagination, while actin-generated forces regulate the degree of pit closure. The critical raft size and active force required for complete wrapping of the nanoparticle (NP) are also found. Moreover, there exists an energy-based competition between raft size and NP stiffness: under raft-deficient conditions, stiffer NPs are preferentially wrapped, whereas under raft-sufficient conditions, softer ones are favored due to their lower elastic energy cost. These findings imply that cells may fine-tune endocytic efficacy and metabolic economy by modulating raft aggregation states. This work provides a foundational theoretical framework for understanding the mechanics of actin-assisted, lipid raft-dependent endocytosis.