Characteristic lengths of transmembrane peptides controlling their tilt and lateral distribution between membrane domains.

Lipids and proteins of plasma membranes of eukaryotic cells are supposed to form protein-lipid domains, characterized by a different molecular order, bilayer thickness, and elastic parameters. Several mechanisms of preferable distribution of transmembrane proteins to the ordered or disordered membrane domains have been revealed. The mismatch between the length of the protein transmembrane domain and hydrophobic thickness of the lipid bilayer is considered to be an important driving force of protein lateral sorting. Utilizing the continuum theory of elasticity, we analyzed optimal configurations and preferable membrane domains for single-pass transmembrane peptides of various hydrophobic lengths and effective molecular shapes. We obtained that short transmembrane peptides stand perpendicularly to the membrane plane. The exceedance of a certain characteristic length leads to the tilt of the peptide. This length depends on the bilayer thickness. Thus, in the membrane with coexisting ordered (thicker) and disordered (thinner) phases tilting of the peptide in each phase is governed by its individual characteristic length. The lateral distribution of the peptides between ordered and disordered membrane domains is shown to be described by two additional characteristic lengths. The exceedance of the smaller one drives the peptide towards a more ordered and thicker membrane, while the exceedance of the larger characteristic length switches the preferable membrane domain from ordered and thicker to disordered and thinner. Thus, membrane proteins with long enough transmembrane domains are predicted to accumulate in the thinner disordered membrane as compared to the thicker ordered bilayer. For hourglass-like and barrel-like shaped transmembrane peptides the specific regime of sorting was obtained: the peptides distributed almost equally between the phases in a wide range of peptide lengths. This finding allowed explaining the experimental data on lateral distribution of transmembrane peptide tLAT.