Research Projects

Elastin-like polypeptides (ELPs) are a class of artificial biopolymers derived from the hydrophobic domain of tropoelastin, a precursor of an extracellular matrix protein, Elastin. ELPs are generally characterized by a pentameric repeat unit Val-Pro-Gly-Xaa-Gly (VPGXG) where the guest residue X can be any amino acid except proline. At a lower critical solution temperature (LCST), similar to tropoelastin, ELPs show a phase transition behaviour, known as liquid-liquid phase separation (LLPS), which leads to the formation of an insoluble coacervate phase (globule-like structure) from a solvated phase (coiled-like chains). The formation of coacervates as well as the transition temperature, sometimes described as Tc, mostly depend on the polymer sequence length (or molecular weight), concentration of ELPs, and the hydrophobicity of the guest residue X. Apart from these primary stimuli, several external stimuli, such as ion specificity and concentrations, pH, pressure, cosolutes and cosolvents, presence of denaturants, etc., also appreciably affect the transition temperatures (Tc) and the phase separation of ELPs. These multiple stimuli-responsive behaviours, along with other additional characteristics, such as biodegradability, precise control over tunable copolymerisation, complex self-assembled structures, and recombinant peptide synthesis, make them highly preferable for a wide range of applications, such as tissue engineering, drug delivery, protein folding and purification, etc. In this project, we want to employ the coacervation of engineered ELPs in the thermal targeted delivery of small drugs to solid tumors. This can improve the therapeutic index of the drugs through their encapsulation in the macromolecular carriers. While the encapsulation of drugs by the coacervates of ELPs has been extensively investigated, experimental techniques face limitations in characterizing the molecular details of coacervates. Alternatively, theoretical methods, such as molecular dynamics (MD) simulations, offer avenues to explore coacervate properties. However, observing phase separation behaviours in explicit solvents surpasses the capabilities of these simulations due to the need for numerous polymer chains, solvent and drug molecules, and extended simulation times to replicate coacervate-like phenomena. To tackle the challenges posed by all-atom models, coarse-grained MD (CGMD) simulations have been utilized across various materials and biomolecular systems, enabling simulations to explore phase separation behaviours of polymers in explicit solvents while enhancing time and length scales. Our project mainly addresses the idea of exploring the targeted drug delivery by ELP coacervates using CGMD simulations. This proposed idea is just the tip of the iceberg in this field and will help further extend the applicability of theoretical studies of ELP-based drug delivery using different systems.