Study of the permeability of cellular membranes using proteoliposomes

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Permeability is the passage of a chemical compound through a biological barrier such as the skin, the pulmonary epithelium or the gastrointestinal tract. In addition to these external barriers, internal barriers also exist limiting the transfer of compounds between the different compartments of the body like the blood, the central nervous system and the organs. These barriers are the natural defenses of the organism against chemical threats, but at the same time they cannot be completely impermeable as nutrition, breathing and excretion are essential physiological functions. Permeability has a impact in multiple fields of science like nutrition, drug absorption and distribution as well as toxicology.At the cellular level, permeability of a compound is regulated by two mechanisms. The first mechanism is passive diffusion of the compound through the cellular membrane. This mechanism depends on the physicochemical properties of the compound. It is easy to study passive diffusion using simple artificial membranes. The second mechanism is named active transport. Membrane transport proteins can extract specific compounds from one side of the membrane and carry them to the other side. To study this process in the laboratory, cellular models or living cells are typically required. Indeed, active transport requires part of the cellular machinery to work. Simple artificial membranes cannot model active transport.We propose to study active and passive diffusion using novel artificial vesicles, namely proteoliposomes. Proteoliposomes are artificial and non-cellular vesicles resembling living cells. Specific proteins can be included in their membrane to enable active transport. Such tools will facilitate the study of permeability including active transport and passive diffusion using non-cellular models.The challenges of this research includes the extraction and purification of membrane transport proteins while maintaining their activity as well as the design of a library functional proteoliposomes. These challenges lie in the field of natural science and engineering. After the five years covered by this application, the knowledge achieved on transport membrane proteins and proteoliposomes could be translated into additional projects such as the conception of integrated microfluidic devices or even the design of non-cellular models of multidrug resistant cancers.