Exploring Membrane Topology Transformations using Polymer Field Theory
Russell Spencer (University of Göttingen)
Membrane remodeling, including fusion and fission, plays a crucial role in various cellular processes. However, understanding the intricacies of these topological changes can be challenging due to the involvement of large-scale membrane rearrangements and their sensitivity to small-scale molecular behavior. Moreover, these remodeling events face significant free-energy barriers that necessitate the presence of catalytic proteins. In this work, we utilize self-consistent field theory (SCFT) in combination with the string method to identify the Minimum Free Energy Path (MFEP). We thereby determine the most probable pathway for specific remodeling transitions implicated in cellular signaling and organelle division. This approach has allowed us to discover a new pathway by which the fusion of membranes may catalyze their fission. Furthermore, we extend conventional SCFT methods, introducing proteins inspired by the dynamin family. These proteins facilitate fission by constricting membrane tubes. We find that the free energy barrier to fission depends strongly on membrane tension and constriction. In addition to simply constricting the membrane, dynamin’s PH domains are inserted between lipid head groups, inducing membrane distortion. Our results emphasize the crucial role of this distortion in reducing the free energy barrier to fission. This research sheds light on the underlying mechanisms of membrane remodeling and provide insights into cellular processes involving topological changes.