Lipid membranes are crucial components of the cellular architecture. In addition to their primary function as spatial organizers of the cellular elements, these structures host many different proteins, and as such they are involved in a myriad of metabolic and signalling pathways. Consequently, the cell’s plasma membrane plays a central role in cellular adaptation, homeostasis, and disease. The active contribution of the plasma membrane to the cell’s activity arises from the intricate molecular interactions between the membrane components, which are ultimately reflected in the membrane’s mechanical behaviour. As such, there has been a growing interest in understanding how the biophysical properties of the cell’s lipid membrane are affected by pathogenic stress.
In this thesis, the relationship between the membrane’s molecular structure and its mechanical behaviour has been studied by combining the unique capabilities of in-house synthesised molecular rotors (fluorescent molecules capable of reporting on their surrounding microviscosity) with advanced fluorescence spectroscopy and microscopy, together with X-Ray diffraction characterisation. Following this approach, it has been possible to quantify how lipid packing and organization changes under mechanical load, under oxidative stress, and in the presence of atherogenic trans-fatty acids.
The results from this work prove how changing the membrane’s composition can tune the membrane’s mechanics, leading to a non-classical behaviour; how peroxidation can induce viscoelastic uncoupling and lipid clustering; and how the presence of trans-fatty acids hinders the membrane’s adaptation under tension. Overall, the results presented in this thesis highlight the tight interplay between the membrane ‘s composition and its mechanical behaviour and aims to encourage further research in the field, which will pave the way towards a better understanding of disease.