Transmembrane (TM) proteins interact closely with the surrounding membrane lipids. Lipids in the vicinity of TM proteins were reported to have hindered mobility, which has been associated with lipids being caught up in the rough surface of the TM domains. These reports, however, neglect one important factor that largely influences the membrane behavior - electrostatics of the TM peptides that are usually positively charged at their cytosolic end. Here, we study on the example of a neutral and a positively charged WALP peptide, how the charge of a TM peptide influences the membrane. We investigate both its dynamics and mechanics by: (i) time dependent fluorescent shift in combination with classical and FRET generalized polarization to evaluate the mobility of lipids at short and long-range distance from the peptide, (ii) atomic force microscopy to observe the mechanical stability of the peptide-containing membranes, and (iii) molecular dynamics simulations to analyze the peptide-lipid interactions. We show that both TM peptides lower lipid mobility in their closest surroundings. The peptides cause lateral heterogeneity in lipid mobility, which in turn prevents free lipid rearrangement and lowers the membrane ability to seal ruptures after mechanical indentations. Introduction of a positive charge to the peptide largely enhances these effects, affecting the whole membrane. We thus highlight that unspecific peptide-lipid interactions, especially the electrostatics, should not be overlooked as they have a great impact on the mechanics and dynamics of the whole membrane.

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences 182 23 Prague 8 Czech Republic

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences 182 23 Prague 8 Czech Republic; Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences 166 10 Prague 6 Czech Republic

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences 182 23 Prague 8 Czech Republic; University of Chemical and Technology Technická 5 Dejvice 160 00 Prague 6 Czech Republic

J Heyrovský Institute of Physical Chemistry of the Czech Academy of Sciences 182 23 Prague 8 Czech Republic; Zernike Institute for Advanced Materials Rijksuniversiteit Groningen Nijenborgh 4 9747 AG Groningen the Netherlands

Zernike Institute for Advanced Materials Rijksuniversiteit Groningen Nijenborgh 4 9747 AG Groningen the Netherlands

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