Cell membrane is primarily composed of about five-nanometers-thick lipid bilayer and defines the physical boundaries of all living cells. It is through this thin layer the cells interact with their physical environment and perform many critical activities like endocytosis, exocytosis, ion-transport, cell-cell communication and cell division. Therefore, understanding the complex hierarchical structure and dynamics of lipid membrane is an essential ingredient to precisely control these vital processes. Biological membranes are in contact with extracellular matrices (ECM)- complex viscoelastic media primarily made of flexible and semi-flexible polymers. Relaxation of the polymers occurs at time scales comparable to those of membrane undulations; it is expected that the lipid motion as well as membrane fluctuations are coupled dynamically. As a result, the membrane dynamics can be altered externally by modulating the viscoelastic properties of the ECM. However, most of the studies so far have been performed on membranes that are isolated from their native environment and embedded in simple solvent media. The overall objective of this EU-funded project entitled ‘Engineering Extracellular Matrices for Controlling Structure and Dynamics of Lipid Bilayer Membranes’ (EXTREME) is to understand, at the fundamental level, how the elasticity of ECM modifies the structure and dynamics of lipid membranes. For this purpose, we used unilamellar lipid vesicles (liposomes) as model artificial cells, and aqueous poly(ethylene glycol) solutions and hydrogels of varying stiffnesses to mimic the viscoelastic properties of the embedded media. By using various state-of-the art characterization techniques, we were able to experimentally correlate, for the first time, the viscoelastic properties of the embedded media and multiscale dynamics of vesicles, from microviscosity in bilayer to bulk diffusion. The results show that, unlike the conventional cell specific chemistry-based approaches, the membrane fluidity can be controlled by engineering the ECM media and opens up exciting new possibilities for developing efficient drug-delivery mechanism and membrane based lipid therapies.
The project achieved its primary objectives and milestones, with relatively minor deviations due to Covid-19 pandemic. With this Action, the experienced researcher gained experience in new techniques, become more skilled in multidisciplinary research areas, dissemination of scientific results, supervising a graduate student, knowledge transfer and management of a research group.
