Supported Lipid Membranes and Their Use for the Characterization of Biological Nanoparticles

Doctoral thesis, 2020

Many diseases threaten our well-being, including cancer, viral infections and neurodegenerative diseases. These diseases are often debilitating, having both societal and personal cost, and can ultimately lead to significant suffering and premature death. Cells are the building blocks of all life forms on earth and are therefore at the epicenter of all processes that maintain or threaten the health of an individual. Each cell is equipped with a biological membrane which contains its processes and protects it from outside influences. Furthermore, the membrane also contains various small molecular channels and “hooks” which enable communication with its surrounding environment or other cells. Millions of molecules are responsible for the communication with the nearest neighbors, and this complexity is a prerequisite for life; however, it can also be exploited by bacteria and viruses to introduce disease-causing material into the cells. For example, viruses, which are often also enclosed by a membrane, have evolved to hijack these processes for their own gain by hooking themselves to the cell membrane, transferring their own genetic information into cells to turn them into virus factories. Comparable to viruses, other similarly sized biological particles, about 1000-times smaller than the diameter of a human hair, have also been observed to transfer genetic information between cells, but rather than causing disease, they fulfill key biological functions. These particles can be found in all biological fluids, including blood, urine and saliva. It is clear from these exemplary mechanisms that they are a highly efficient way of affecting target cells and as such, there is a need to study these small particles to understand their complex interactions with cellular membranes. Furthermore, aided by an understanding of these interactions, new drugs targets could be identified and addressed, to take advantage of these particles to cure diseased cells or even destroy cancer cells. Finally, yet importantly, due to their presence in many bodily fluids, the hope for early detection of slow progressing diseases, rests on these particles.

In this work, I have investigated these small particles and their interactions with simplified cell membrane models. Specifically, I have studied how these model membranes react with common materials used in implants and as drug-carriers, but also how the membranes interacted with relevant drugs themselves. It became apparent, that the model membrane system can aid the development and testing of future more advanced means of drug-delivery. Secondly, I studied small virus-like particles to help characterize their size and membrane properties for further usage in diagnostics and drug discovery applications. This was all made possible by advanced microscopy techniques and small microfluidic devices.

It is my hope that the insights gained from this research will bring us one step closer to discovering the early stages of disease progression and to better address debilitating diseases through more efficient delivery of new drugs.