The lateral mobility of proteins within cell membranes is usually thought to be dependent on their size and modulated by local heterogeneities of the membrane. Experiments using single-particle tracking on reconstituted membranes demonstrate that protein diffusion is significantly influenced by the interplay of membrane curvature, membrane tension, and protein shape. We find that the curvature-coupled voltage-gated potassium channel (KvAP) undergoes a significant increase in protein mobility under tension, whereas the mobility of the curvature-neutral water channel aquaporin 0 (AQP0) is insensitive to it. Such observations are well explained in terms of an effective friction coefficient of the protein induced by the local membrane deformation.Brownian motion | Saffman-Delbrück | internal membrane structure | drag force | micropipette aspiration B rownian motion plays an essential role in biological processes. Since the pioneering experiments of Perrin (1), the observation of diffusing objects has emerged as a mean to extract the rheological properties of the surrounding medium or the probe particle size. The theoretical investigation of diffusion of proteins within membranes has been studied widely going back to P. G. Saffman and M. Delbrück (SD). They investigated the hydrodynamic drag acting on a membrane inclusion when the membrane is described as a 2D fluid sheet of viscosity μ m embedded within a less viscous fluid of viscosity η (2). In this theory, the diffusion coefficient D 0 in the limit of a large viscosity contrast between the membrane and bulk fluid is given by:The length ℓ = μ m =η is the length scale over which flow is generated within the bilayer by the inclusion, k B T is the thermal energy, and γ is Euler's constant. This model predicts a logarithmic dependence of D 0 on the protein radius a p , which has been confirmed for some in vitro experiments on membranes containing transmembrane proteins (see ref.3 and references therein). In contrast, the experiments of Gambin et al. (4) showed significant deviations from the SD theory. A possible origin for the discrepancy observed by Gambin et al. (4) is the significant local membrane deformation due to the interaction between the inclusion and the lipid bilayer (5). Naji et al. suggested in ref. 6 that inclusions experience additional dissipation, either due to internal flows within the membrane or to additional fluid flows produced by the deformed membrane. This work triggered a number of theoretical studies investigating the coupling of inclusion proteins with the membrane that had been pioneered by the Seifert's group (see ref. 7 and references therein). Such studies have systematically gone beyond the SD model by including additional effects (8-12). So far, a thorough verification of these ideas has not been attempted. To investigate the effect of the protein-lipid coupling on the protein mobility, we study its dependence on membrane tension, because this parameter affects the local membrane deformation.In this work, we compare the mobility of t...