A hydrophobic mismatch between protein length and membrane thickness call lead to a modification of protein conformation, function, and oligomerization. To study the role of hydrophobic mismatch, we have measured the change in mobility of transmembrane peptides possessing a hydrophobic helix of various length d(pi), ill lipid membranes of giant vesicles. We also used a model system where the hydrophobic thickness of the bilayers, h, call be tuned at Will. We precisely Measured the diffusion coefficient of the embedded peptides and gained access to the apparent size of diffusing, objects. For bilayers thinner than d(pi) diffusion coefficient decreases, and the derived characteristic sizes are larger than the peptide radii. Previous studies Suggest that peptides accommodate by tilting. This scenario was confirmed by ATR-FTIR spectroscopy. As the membrane thickness increases, the value of the diffusion coefficient increases to reach a maximum at h approximate to d(pi). We show that this variation ill diffusion Coefficient is consistent with a decrease in peptide tilt. To do so, we have derived a relation between the diffusion coefficient and the tilt angle, and We used this relation to derive the peptide tilt from our diffusion measurements. As the membrane thickness increases, the peptides raise (i.e., their tilt is reduced) and reach all upright position and a maximal mobility for h approximate to d(pi). Using accessibility measurements, we show that when the membrane becomes too thick, the peptide polar heads sink into the interfacial region. Surprisingly, this "pinching" behavior does not hinder the lateral diffusion of the transmembrane peptides. Ultimately, a break in the peptide transmembrane anchorage is observed and is revealed by a "jump" in the D values.