Control Over Peptide Self-assembly/ Disassembly Towards Coacervates and Organic-Inorganic Functional Hybrids

Abstract

Natural biomolecular systems have highly sophisticated hierarchical organization, fundamental for cellular functioning. Replicating such structures and functions in an artificial setting requires utilizing nature’s molecular toolbox like biology does i.e., out-of-equilibrium supramolecular self assembly. In that regards, proteins and short peptides assemblies have garnered attention as system of choice to instil biomimetic structure and function. Aggregation behaviour of amyloids and prion-inspired fragments facilitate designing complex multi-component active materials with living supramolecular polymerization. However, mimicking unique traits of natural systems by mere match of chemical and sequence space is very challenging. In chapter 2, we demonstrate an elegant orthogonal self-assembly/dis-assembly strategy of an amyloid-inspired peptide with interplay of gold nanoparticles and cysteine. Such gold nanoparticles can be spatiotemporally decorated along the fiber with a robust polydopamine coating. Development of such strategy is essential for advancements in materials science, molecular biology, nanotechnology and precision medicine. In chapter 3, we introduced point mutation in our peptide sequence in an effort to study its influence on the pathway dynamics. We observed a cascade of interesting phenomena arising out of the sticky interactions from the guanidinium switch. Highly dynamic competing structures offered a coexistent fiber-droplet assembly state reminiscent of secondary nucleation-dissociation of amyloids. We leveraged the polydopamine reinforcement in this case to shift the order-disorder spectrum towards robust ordered fibers. We anticipated the prebiotic informational role of amyloids and their low complexity domains towards the development of protocell mimics. In chapter 4, we explore a scrambling approach in our synthetic peptides resulting in re-entrant liquid-liquid phase separation forming peptide coacervates. Our biomimetic synthetic methodology enables encompassing the extremes of order disorder spectrum towards compartmentalization. Finally, we developed a series of peptide amphiphiles with varying hydrophobicity as template for fabricating organic-inorganic functional hybrids (Chapter 5). We harnessed the structural differences guided by temporal effect and mechanical strength to dictate the bioactivity and cellular response of peptide-templated bioactive glass. Interestingly, these composites exhibited exceptional bone extracellular matrix mimicking surface chemistry and mechanical response in terms of load-bearing and strain-stiffening. Biomimetic peptide self-assembly thus paves way for mimicking the complex mechano-chemical signaling processes of cells and biopolymers for advancements in material chemistry in the future.