Unsymmetric or hybrid detergents for membrane protein structural study

Abstract

Detergent micelles are widely used as a membrane-mimetic system for membrane protein extraction, isolation and structural study. Many recently developed detergents feature multiple tail and head groups, with architectures that are symmetric (i.e. the same alkyl chain) and non-hybrid (single head group type). Further diversification has involved incorporating structural differences in the tail groups (unsymmetric), head groups (hybrid), or both head and tail groups (unsymmetric hybrid). In this mini-review, we introduce these novel detergents, focusing on the relationships between their structural features, physical properties and performance in membrane protein applications. The detergent design strategy utilizing unsymmetric/hybrid structures expands the detergent repertoire and the detergent structure–property-efficacy relationships presented offer valuable design guidelines, collectively advancing membrane protein research. © 2025 Elsevier Ltd