Membrane partitioning: distinguishing bilayer effects from the hydrophobic effect

Area of Science:

• Biochemistry
• Physical Chemistry
• Membrane Biophysics

Background:

• The transfer of nonpolar solutes to lipid bilayers often shows a large negative enthalpy, contradicting the expected positive entropy from the hydrophobic effect.
• This has led to the concept of a "nonclassical" hydrophobic effect, questioning the role of the classical hydrophobic effect in bilayer partitioning.

Purpose of the Study:

• To investigate the role of the hydrophobic effect in solute partitioning into lipid bilayers.
• To determine if the classical hydrophobic effect drives partitioning despite observed negative enthalpy changes.
• To assess the adequacy of bulk-phase measurements for describing bilayer partitioning.

Main Methods:

• Measuring heat capacity changes associated with the partitioning of tryptophan side-chain analogs.
• Comparing partitioning into lipid bilayers versus bulk cyclohexane.

Main Results:

• The hydrophobic effect plays a critical role in lipid bilayer partitioning, irrespective of the significant negative enthalpy.
• Bulk-phase measurements do not accurately reflect the processes occurring during bilayer partitioning.

Conclusions:

• The hydrophobic effect is a key driver for nonpolar solute partitioning into lipid bilayers.
• Experimental methods focusing on bilayer properties are essential for accurate analysis.
• The described approach can be applied to study various biologically relevant molecules.