Abstract
What is life? We still lack definitive answers. Since the cell is the fundamental building block of all life forms, we try to understand the origin of life and the organization of modern cells by making small compartments (also called “protocells”) with life-like properties from the bottom up. In this thesis, we used coacervates and liposomes, which serve as mimics of the membraneless organelles and membrane-bound compartments, respectively, as basic units to build protocells via new routes. In Chapter 1, we give a brief history of protocell research and describe different models that are currently being studied. In Chapter 2, we develop model systems for hierarchically organized condensed liquid droplets formed by liquid-liquid phase separation in biological systems. In Chapter 3, we investigate coacervates formed by nucleoside triphosphates with different cationic peptides as a function of temperature. Membraneless and membrane-bound organelles in living cells do not exist independently. Therefore, in Chapters 4 and 5, we combine coacervates and liposomes to explore their interactions. In Chapter 4, we prove that coacervate droplets can wet and deform lipid membranes and be taken up via endocytosis, depending on their attraction to the membrane and the balance between the membrane and coacervate surface tension. In Chapter 5, we demonstrate that the ability of coacervates to sequester lipids determines their ability to penetrate lipid membranes. The electrostatic interaction between the coacervate and membrane helps form the initial contact necessary for this process. Finally, in Chapter 6, we put our results into a broader perspective of protocells and synthetic cells. Altogether, this thesis is a study of coacervates interacting with each other or interacting with the membranes of liposomes, which sheds light on the fundamental physicochemical principles of building protocells and paves the way for utilizing coacervates as delivery vehicles to deliver cargoes.
