TY - JOUR T1 - A continuum membrane model predicts curvature sensing by helix insertion JF - bioRxiv DO - 10.1101/2021.04.22.440963 SP - 2021.04.22.440963 AU - Yiben Fu AU - Wade F. Zeno AU - Jeanne C. Stachowiak AU - Margaret E. Johnson Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/04/23/2021.04.22.440963.abstract N2 - Protein domains, such as ENTH (Epsin N-terminal homology) and BAR (bin/amphiphysin/rvs), contain amphipathic helices that drive preferential binding to curved membranes. However, predicting how the physical parameters of these domains control this ‘curvature sensing’ behavior is challenging due to the local membrane deformations generated by the nanoscopic helix on the surface of a large sphere. To overcome this challenge, we here use a deformable continuum model that accounts for the physical properties of the membrane and the helix insertion to predict curvature sensing behavior and is in good agreement with existing experimental data. Specifically, we show that the insertion can be modeled as a local change to the membrane’s spontaneous curvature,. Using physically reasonable ranges of the membrane bending modulus к, and a of ∼0.2-0.3 nm-1, this approach provides excellent agreement with the energetics extracted from experiment. For small vesicles with high curvature, the insertion lowers the membrane energy by relieving strain on a membrane that is far from its preferred curvature of zero. For larger vesicles with low curvature, however, the insertion has the inverse effect, de-stabilizing the membrane by introducing more strain. The membrane energy cannot be directly predicted analytically, due to shape changes from surface relaxation around the anisotropic insertion. We formulate here an empirical expression that captures numerically calculated membrane energies as a function of both basic membrane properties (bending modulus к and radius R) as well as stresses applied by the inserted helix ( and area Ains). We show that the shape relaxation energy has a similar magnitude to the insertion energy, with a strong nonlinear dependence on . We therefore predict how these physical parameters will alter the energetics of helix binding to curved vesicles, which is an essential step in understanding their localization dynamics during membrane remodeling processes.Competing Interest StatementThe authors have declared no competing interest. ER -