Influences of the Hydrophobic Environment on the Structure and Function of Membrane Proteins and Development of Innovative Surfactants Called Amphipols

Abstract

Membrane proteins (MPs) exhibit a broad range of activities, which are crucial for cell survival. Understanding their molecular mechanisms generally requires their extraction out of membranes and their purification. Solubilization and isolation are usually carried out using detergents, which disrupt the membrane and adsorb onto the hydrophobic surface of the transmembrane domain of MPs, keeping them water-soluble. Detergents, however, tend to inactivate most MPs more or less rapidly, because they compete with stabilizing intra- and intermolecular interactions. The extent of this problem varies from one detergent to another but also considerably depends on the nature of MPs, creating a bias in our understanding of their structure and function in favor of the most robust MPs.Specially designed amphipatic polymers called 'amphipols' (APols) have been developed with the view of improving the stability of MPs in aqueous solutions. The first APols to have been synthesized comprise a poly-acrylic acid backbone onto which octylamine and isopropylamine side chains have been randomly grafted. The solution properties of APols and of the complexes they form with MPs have been investigated in some details (1). It has been demonstrated that APols are promising surfactants for biochemical and biophysical studies of MPs, because they form with MPs small and compact water-soluble complexes while improving the stability of the MPs they interact with. The rich chemistry of APols also allows modifications and labeling, generating a library of molecules that expand the scope of APol applications in both basic and applied research. Among the many novel surfactants developed to replace classical detergents, APols present the advantage of being remarkably easy to use (http://www.ibpc.fr/popot/amphipol/).(1) Popot et al., Amphipols from A to Z (2011) Annu. Rev. Biophys. 40:379-408.