Theoretical and Experimental Investigation of Liquid-Liquid Phase Separation: Characterizing Elastin-Like-Polypeptides

This dissertation develops and validates a semi-empirical Flory–Huggins-based interaction model, combined with Cahn–Hilliard simulations, for predicting multi-component liquid–liquid phase separation (LLPS) in elastin-like polypeptide (ELP) systems. Equilibrium droplet compositions, measured using a PDMS-based microfluidic device, enabled direct parameterization of interaction coefficients. The model was applied to generate phase diagrams and assess composition dependence in ternary mixtures. Cahn–Hilliard simulations were conducted to explore potential phase morphologies under different interfacial conditions. Multi-component Lattice Boltzmann simulations were implemented to model droplet morphology evolution under varying interfacial and diffusive parameters, reproducing experimentally relevant morphologies. A three-phase wetting study revealed conditions for selective wetting and phase encapsulation, with implications for multi-phase compartment design. These results collectively establish a quantitative link between experimentally accessible parameters and predictive phase behavior in ELP mixtures, offering a platform for rational engineering of multi-phase condensates.