Hydrophilic lipophilic balance: A lighthouse parameter for designing efficient detergents in membrane protein...

Since the 1970s, the hydrophilic lipophilic balance (HLB) has been widely recognized as a key parameter for evaluating the effectiveness of detergents across various fields, including membrane protein (MP) research. Detergents play a crucial role in the structural and functional characterization of membrane proteins: they disrupt the lipid bilayer, provide a stabilizing environment that maintains both protein solubility and native conformation, and facilitate subsequent crystallization. In this review, we trace the integration of the HLB concept into detergent development for membrane protein studies over the past 55 years. We revisit foundational work demonstrating that effective detergents span a wide range of HLB values. We highlight recent advances involving diverse detergent classes, including hydrogenated, fluorinated, cyclic, and linear molecules, to illustrate the continuing relevance of the HLB as a guiding parameter in detergent design. HLB values of well-established and widely used detergents are put into perspective alongside those of recently synthesized compounds to offer valuable insights into their performance in membrane protein studies and guide the rational design of next-generation detergents. Finally, we discuss how chemists and biochemists strategically apply the HLB parameter to optimize detergent design for membrane protein research.