Director of the Laboratoire de chimie des polymères organiques (LCPO) at the Université de Bordeaux-CNRS, Sébastien Lecommandoux is a physical chemist. He is interested in the synthesis and self-assembly of complex macromolecules, and in understanding the structural and functional properties of matter to design nature-inspired polymers that provide solutions in fields such as biomaterials and nanomedicine.
In 2024-2025, he has been invited to occupy the Technological Innovation Liliane Bettencourt Annual Chair at the Collège de France.
In the public eye, the notion of polymer is often associated with plastics, or with polluting materials that have replaced more natural substances in our daily lives. However, it is a very broad chemical concept ; a polymer is a large molecular structure made up of sub-units capable of interacting with each other and having a wide range of properties. These macromolecules hold the key to solving many of society's problems in the fields of materials, energy, medicine, pharmaceuticals and cosmetics. Since the 1990s, Sébastien Lecommandoux, physical chemist and Director of the CNRS Organic Polymer Chemistry Laboratory in Bordeaux, has been interested in understanding these materials and applying them in a number of fields, including life sciences.
Sébastien Lecommandoux gradually developed his interest in science during his studies. From optics to biology, his curiosity led him to consider several choices, but it was finally chemistry that set his sights, spurred on by his childhood love of pastry-making, inherited from his family of bakers. " I see chemistry as the act of creating and shaping matter; atoms and molecules are assembled with the idea of producing an object endowed with particular properties ", he explains. His doctorate in physical chemistry, which focused on liquid crystals, was an extension of his thinking, and from then on his work combined the synthesis of materials with the study of their organizational properties.
A code for building polymers
During his post-doctorate at the University of Illinois at Urbana-Champaign, in the United States, he turned his attention to the notion of self-assembly. This is the process by which a system composed of disorganized elements assembles and structures itself in an autonomous, spontaneous and programmed manner. This may involve, for example, several small molecular or macromolecular segments interacting with each other to organize themselves into ordered structures on a larger scale. " The beauty of this concept is that we can encode information on a molecular scale that will be transcribed on a larger scale in terms of organization and functionality," he notes. In other words, if researchers have a good understanding of how the various molecular elements interact with each other, they can, by injecting the right information in the right place, influence the course of the self-assembly process to obtain a product with the desired properties. This information, in the form of attractive and repulsive interactions, enables a system to reach a state of equilibrium, and thus to have a predefined structure and order. This is how nature structures cell membranes, for example, or how we obtain nanoscale polymers with specific optical, electronic, mechanical, adhesion or separation properties.
Back in France after his post-doctorate, Sébastien Lecommandoux set out in search of polymers that could emulate the properties of the liquid crystals he had been working with until then. He turned to polypeptides, small chains of amino acids similar to proteins. As some of these synthetic polypeptides can adopt a helix shape, he first used them as models for forming hierarchical structures in matter, and gradually realized the potential applications of these polymers strongly inspired by living matter beyond their structuring capacity, notably in the fields of pharmaceuticals and nanomedicine. One of the major challenges in these fields is how to deliver a therapeutic molecule to a precise point in the human body, at a precise time
From liposome to polymersome
Sébastien Lecommandoux became interested in this question, and thanks to his admission to the Institut Universitaire de France in 2007, he was able to devote his research time to developing a major project that he is still pursuing today, almost twenty years later. His goal was to set up a transdisciplinary team to work on the development of new polymers for transporting active substances and delivering them for therapeutic purposes: the "Polymer self-assemblies and life sciences" team at the CNRS Organic Polymer Chemistry Laboratory (LCPO) in Bordeaux was born. " We really want to transfer the knowledge and know-how developed in our research as far as possible, which means to industry, but also and above all to hospitals ", he explains.
In this context, he is working on the development of polymersomes. These molecular structures are named by analogy with liposomes, vesicles (or shells) composed of a lipid membrane that can encapsulate substances and contain them for transport to a given point, where they will be released. Liposomes, already widely used in the medical world, can solve a large number of vectorization and active ingredient release problems, but not all of them. " Polymersomes, built from polymers, extend the range of properties made accessible by liposomes, adding a high degree of modularity," recounts the physical chemist. One of the great advantages of these polymersomes, compared with their lipid counterparts, is that they can be particularly stable. Although this field of research originated in the early 2000s, Sébastien Lecommandoux's team was among the first to work with bio-inspired polypeptide-based systems, in a logic of biomimicry.
Finding inspiration in the living world
in polymer chemistry, it's possible to synthesize highly sophisticated structures with a wealth of information," explains Sébastien Lecommandoux. But for our designs to find application in humans, they must not be too complex to develop at industrial or hospital level." The challenge is no small one, for despite this necessary simplicity, the criteria can be numerous and contradictory. Polymers must be stealthy, i.e. they must not interact with anything in the body, as this could generate undesirable and deleterious immune or inflammatory reactions. However, they do need to be able to interact, specifically targeting their destination, such as a tumor cell, for example, in a cancer treatment context.
this is where the notion of biomimicry comes in," notes the physical chemist. To find a solution to these constraints, we have to draw inspiration from what is done in the living world, and integrate it into our synthesis approaches. " Indeed, in biology, many processes and structures result from self-assembly phenomena. This is the case, for example, of the biological membranes that delimit our cells. Researchers are therefore focusing on biological polymers with highly specific targeting capabilities: polysaccharides - chains of simple sugars - polypeptides or proteins, assembled to form polymersomes that mimic the natural properties found in living organisms. " We have to choose ingredients capable of integrating all this information without producing hyper-complex structures. But the world of Dynamics of Living Systems is dynamic and constantly on the move. So, if we want to mimic it and interact with it, we need to develop systems that are just as dynamic. " When a particle interacts with a cell, the latter can reconfigure itself, for example, by concentrating its receptors in one place on its membrane. The creation of organized, functional and dynamic systems is therefore one of the current challenges of his work.
Working at the interface
Although Sébastien Lecommandoux's research is first and foremost fundamental, he is always keen to keep a distant view in his work, particularly when it comes to medical applications. The concepts and ideas he develops with his team are based on listening to and understanding biological issues, to which he intends to respond by developing appropriate chemical systems. " By always working as closely as possible to those involved in the clinical world, we can better understand their issues, and innovate more effectively from a fundamental point of view, always keeping in mind a transfer to a useful application for society." Over the years, he has built polymersomes capable of reacting to pH, temperature or the presence of enzymes; others, which respond to light, magnetic fields or X-rays. Today, he is contributing to this technology transfer as co-founder of the Doxanano company, whose aim is to develop polymersome technology for cancer treatment.
All these developments have been made possible by a deeply transdisciplinary team, combining specialists in macromolecular synthesis, protein engineering, self-organization, nanostructuring, pharmaceutical aspects and, increasingly, biology. when you're working on intrinsically transdisciplinary themes, you can't totally master each field 100%," emphasizes Sébastien Lecommandoux. What counts is to be able to understand the very essence of the scientific problems to be solved, to decode them in your own language and to integrate a wide range of skills to solve the issues you are tackling." This same collaborative approach is reflected in his dialogue with industry. To strengthen these ties, the physical chemist helped set up the first joint laboratory between L'Oréal and the CNRS, with the aim of developing biosourced and biodegradable polymers for cosmetic use. He has been its academic director since its foundation in 2018.
The true face of polymer chemistry
For the year 2024-2025, Sébastien Lecommandoux has been invited to occupy the Technological Innovation Liliane Bettencourt Annual Chair at the Collège de France. An appointment he accepts with great humility, particularly in view of the prestige of his predecessors. It's also a rich opportunity for him to exchange ideas with colleagues from a wide variety of disciplines. i'm fundamentally convinced that, by taking a small step aside and looking at what's going on in other fields, we can make correlations and feed our thinking into our own work," he notes. I want to take advantage of this experience to learn and be even more creative, two fundamental aspects in the life of a researcher. " The physical chemist also relishes the responsibility of passing on his field's knowledge to a wider audience. " There are some important messages to get across, especially for the field of polymers, which, while well known, is sometimes misunderstood. I'd like to be able to show that polymers can be used to create far more interesting and useful materials than just plastics. Polymer science is a science in its own right, with its own challenges, and should be seen as such. It's a field of research at the interface of many fields and, in my approach, understanding nature to create multi-component, multi-scale and dynamic materials is exciting. So many important directions to consider for the design of tomorrow's biomaterials! "
With an eye already set on the future, Sébastien Lecommandoux and his team are now working on developing compartmentalized systems, taking biomimicry one step further. Their idea is to mimic the cell, or at least to partially reproduce the organizational complexity of a cell, as well as its dynamic nature and some of its functions. The aim would be to imagine an artificial cell capable of interacting with real cells to detect, understand and correct its potential dysfunctions, or to design biohybrid organs. A therapeutic approach that underlines the physico-chemist's determination to conduct his research with a distant vision.
Article by William Rowe-Pirra
