TEMPERATURE-DEPENDENCE OF POLYPEPTIDE PARTITIONING BETWEEN WATER AND PHOSPHOLIPID-BILAYERS

Various thermodynamic forces (e.g., the hydrophobic effect, electrosta tic interactions, peptide immobilization, peptide conformational chang es, ''bilayer effects,'' and van der Waals dispersion forces) call par ticipate in the transfer of polypeptides from aqueous solution into li pid bilayers. To investigate the contributions of these forces to pept ide-membrane thermodynamics, we have studied the temperature dependenc e of the water-bilayer partitioning of 4 polypeptides derived from the first 25 amino acid residues in tile presequence of subunit IV of yea st cytochrome c oxidase (Cox IVp) using electron paramagnetic resonanc e spectroscopy, The partitioning of the Cox Np peptides into phospholi pid bilayers increase as the temperature is increased from 3 to 40 deg rees C. The contribution of bilayer surface expansion to the temperatu re-dependent partitioning is estimated to be relatively small and to c ontribute minimally to the increased bilayer binding of the peptides w ith increasing temperature, Thermodynamic analysis of the data shows t hat the transfer of the peptides from water into bilayers at 298 K is driven by the entropic term (-T Delta S-tr) with vaiues ranging from - 6.7 to -10 kcal mol(-1), opposed by the enthalpic term (Delta H-tr) by approximately 4 kcal mol(-1), and accompanied by a change in heat cap acity (Delta C-p) ranging from -117 to -208 cal K-1 mol(-1). Our resul ts indicate that while a variety of forces do, in fact, contribute to the transfer free energies (Delta G(tr)), the major driving force for the water-to-bilayer transfer is the hydrophobic effect.