Amphipols: where from? Where to?

Abstract

I am often asked how the idea of amphipols came about. Now, exactly 20 years later, is perhaps a good time to recount the story. My main field of expertise is membrane biochemistry. The French Centre National de la Recherche Scientifique (CNRS) was originally designed by its founders as a multidisciplinary research organization. Until its recent splitting into several institutes, it offered a particularly favorable environment for scientists of different backgrounds to develop original projects at the interface between their respective fields. In the fall of 1990, Paul Rigny, then director of its Chemistry Department, launched a series of meetings around the theme of ‘‘Organized molecular systems’’, among which membranes feature prominently. Three interdisciplinary round-tables took place that year (chemistry/physics, chemistry/biology, biology/physics), followed, in 1991, by a big meeting in Bordeaux. The meeting itself was very formal and, to me at least, rather boring, but the round-tables were an excellent opportunity to build bridges between communities. I took part in the latter two, and was so interested that I became involved in many kinds of activities at the interfaces between biology, chemistry and physics. I coorganized an international summer school in 1994 in Cargese (Corsica), along with the physicist David Bensimon and the chemist Ludovic Jullien, and took part in or set up various interdisciplinary networks of French laboratories dealing with selforganizing systems, as well as a large CNRS interdisciplinary granting project. In the process, I was exposed to lots of information that have only tenuous connections to biology (including the marvelous properties of clays). Among those were some intriguing stories, such as the immiscibility of hydroand fluorocarbons, or the fact that surfactant micelles can be used to crosslink hydrophilic polymers carrying sparse alkyl chains, with spectacular effects on their rheology. A few years and many shared beers later, some of these systems found their way into membrane biology. The fluoroalkane story developed into a long and friendly collaboration with the chemist Bernard Pucci, of the University of Avignon, with whom we designed and validated a series of fluorosurfactants for handling membrane proteins. The polymer story led to amphipols. In 1994, I was approached by Roland Audebert, from the Ecole Superieure de Physique et de Chimie Industrielles (ESPCI, Paris), a chemist active in the field of amphipathic polymers. Roland had heard me present talks about membrane proteins and their complicated and often contentious relationship with detergents. His idea was to use them as nodes to cross-link hydrophobically modified polymers. Roland knew that some membrane proteins undergo conformational changes upon binding a ligand or detecting light and, although I don’t remember whether we discussed this point or not, I feel certain that he anticipated this could possibly lead to ‘‘intelligent’’ materials that would react to specific stimuli, a subject of great interest to him. I was not particularly thrilled by the idea of using my precious, hard-to-prepare membrane proteins to make gels, but I was keenly interested in exploring alternatives to detergents and their denaturing properties. I countered with the suggestion to make very small and flexible amphipathic polymers that could replace detergents at the surface of membrane proteins, thereby keeping them soluble and, I would like to dedicate this special issue to the memory of Annemarie Weber (1923–2012), inspiring teacher and lifelong friend—J.-L. Popot.