Understanding and controlling lipid membrane dynamics with external agents

Qutbuddin, Yusuf (2025): Understanding and controlling lipid membrane dynamics with external agents. Dissertation, LMU München: Fakultät für Physik

Abstract

Synthetic cells, just like living cells, require a dynamic boundary that can separate what is inside and outside. Lipid membranes remain the most deserving candidates for both living and synthetic cells owing to their elegant chemistry and their dynamic emergent properties. Lipid membranes continue to fascinate and employ chemists and physicists to truly develop a holistic understanding of their behavior. In living cells, lipid membranes are involved in a lot of crucial processes that the cell requires for sustenance and proliferation. However, when these lipid membranes are isolated for use in compartmentalization, in hopes of creating synthetic life, they retain their dynamic potential but lose active agents that manipulate the membranes. Biologists and biophysicists then employ various cell machinery to attempt manipulation of the membranes as desired. Reconstitution of protein machinery in lipid membranes is a vast topic, and a major advantage that bring the lipid systems into the synthetic world is to truly utilize the technological advancements of synthetic chemistry. In this thesis, I have focused on using and developing strategies of manipulating model membranes with the tools accessible to synthetic chemists. These external agents can be passive like macromolecules which spontaneously embed into lipid membranes and exhibit complex interactions with the bilayer. Contrarily, they can be active agents that transfer energy to the lipid bilayers without the need of biological arsenal. I aimed to employ these chemical tools to develop a fundamental understanding of how they act on lipid membranes and the consequences of these interactions from the perspective of the bilayer. It not only accentuates our knowledge on lipid bilayers, but also lays groundwork for future researchers to design better tools for desired outcomes. The projects in this thesis explore both passive and active external agents to induce morphological transitions in model membranes. This work utilizes both supported and free-standing lipid bilayers to systematically characterize the effects of external agents on the mechanical properties of the membrane. Fluorescence microscopy and spectroscopy, including fluorescence lifetime spectroscopy and fluorescence correlation spectroscopy prove to be essential methodologies for studying model membranes. I also focused on advancing available techniques like electrodeformation of vesicles to more complex systems for optimizing their use in synthetic cell studies. This work systematically introduced the world of rotary motors to lipid bilayers, and photoactive compounds hold great promise for being crucial game-changers in synthetic cells. Furthermore, with better surface-engineering and coating strategies, synthetic cells would also become more viable for being used in drug delivery and pharmaceutical industries. This work also highlights the limitations in current technology, posing important open questions and potential future endeavors. Rapid advances in synthetic chemistry, fluorescence techniques and computational power promise to lead researchers to the development of true synthetic cells.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: lipid membrane, rotary motors, glycopolymers, membrane dynamics
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 530 Physik
• Fakultäten: Fakultät für Physik
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 3. Februar 2025
• 1. Bericht­erstatter:in: Schwille, Petra