Abstract:
Single-chain amphiphiles (SCAs) based vesicle systems are endowed with interesting properties like high dynamicity of membranes, making these systems more amenable to molecular/chemical evolution and exciting as stimuli-responsive protocellular compartments. Protocells can be endowed with biomimetic properties such as molecular crowding, growth, division, etc., making them an exciting model of minimal compartments for the understanding of fundamental biophysical and biochemical phenomena of complex life-like systems. Various SCAs with their distinct molecular properties do influence the membranes they form. Given the heterogeneity of the primordial soup, liposomal protocell populations with distinct membrane properties could have been present in the same prebiotic ‘niche’. In this context, we demonstrated how the dynamical interactions amongst distinct protocell populations interacting in the same environment could result in emergent properties like growth, shape deformation and molecular crowding. We characterized this systematically to show that such properties are solely driven by the respective physicochemical properties of the protocell membranes. We also demonstrated how competition and coexistence could simultaneously occur among distinct and interacting protocell populations. We also characterized a novel amphiphile system made of 2-hydroxyoctanoic acid in a prebiotic context. This self-assembled amphiphile system demonstrated here could form unique temperature-tunable compartments in the putative prebiotic soup. Interestingly, this system undergoes self-assembly at highly acidic pH as well ,which is a rare instance for a SCA system. Further, taking advantage of the fundamental properties of different SCA systems, we made inroads to show how an SCA-based hybrid liposomal system could be used for targeted delivery of cargo molecules in vivo. This is triggered by a physiological stimulus of pH change, which in turn drives the tuneability of this system. Specifically, we have been using Drosophila melanogaster as a model system for the targeted delivery of tastants to its middle midgut. In all, the findings discussed in this thesis highlight the relevance of characterizing how the dynamicity of SCA-based membrane systems results in unique biophysical outcomes, thereby allowing us to explore the tunability of these systems for both fundamental and applied research purposes.
