Membrane Remodeling Driven by Shallow Helix Insertions via a Cooperative Mechanism

Helix-membrane interactions are key to membrane deformation and play significant biological roles. However, systematic studies on the mechanisms behind these interactions are limited. This study uses a continuum membrane model to investigate how shallowly inserted helices interact with biological membranes, focusing on membrane deformation and the cooperative effects of multiple helices. Our findings show that even short helices (2 nm in length) can induce anisotropic membrane deformation. Longer helices and deeper insertions result in more significant deformations, and the spatial arrangement of helices affects the nature of these deformations. The perturbation area (PA) and perturbation extent (PE) are quantified to describe membrane deformation, revealing stronger cooperative effects in parallel insertions and more complex deformations in other arrangements. Additionally, membrane properties, such as lipid composition, influence the extent of deformation. In multi-helix systems, we observe local clustering behavior when perturbations are strong enough, with cooperativity varying based on helix length, insertion depth, and membrane composition. This study provides criteria for helix cooperativity, advancing our understanding of helix–membrane interactions and their biological significance in processes like membrane remodeling.