Application of Thermoresponsive Intrinsically Disordered Protein Polymers in Nanostructured and Microstructured Materials

Abstract

Modulation of inter‐ and intramolecular interactions between bioinspired designer molecules can be harnessed for developing functional structures that mimic the complex hierarchical organization of multicomponent assemblies observed in nature. Furthermore, such multistimuli‐responsive molecules offer orthogonal tunability for generating versatile multifunctional platforms via independent biochemical and biophysical cues. In this review, the remarkable physicochemical and mechanical properties of genetically engineered protein polymers derived from intrinsically disordered proteins, specifically elastin and resilin, are discussed. This review highlights emerging technologies which use them as building blocks in the fabrication of highly programmable structured biomaterials for applications in delivery of biotherapeutic cargo and regenerative medicine.

Tuning the Properties of Protein-Based Polymers Using High-Performance Orthogonal Translation Systems for the Incorporation of Aromatic Non-Canonical Amino Acids

“…Similarly, the chemical modification of methionine residues encoded in the guest-residue position in ELPs also enabled the tuning of the LCST ( Kramer et al, 2015 ; Petitdemange et al, 2017 ; Rosselin et al, 2019 ) and triggered the self-assembly of di-block ELPs ( Dai et al, 2021 ). However, until recently, the moderate efficiency of orthogonal translation systems has limited the production of PBPs that contain multiple instances of ncAAs by genetic code expansion, and thereby hindered the analysis of the resulting properties ( Wang et al, 2021 ).…”

Temperature-Responsive Nano-Biomaterials from Genetically Encoded Farnesylated Disordered Proteins

“…Biopolymers with programmable thermoresponse (such as ELPs) are attractive materials for biomedical applications because the temperature can be increased locally as a therapeutic modality while causing minimal damage to healthy tissues. 54 While the effect of amino acid mutations on the liquid–liquid phase separation of proteins is under intense investigation, 55 , 56 our understanding of the effect of lipidation on the phase-boundaries remains incomplete. Given the importance of thermoresponse in biomedical applications, 57 , 58 we used complementary techniques of turbidimetry and DSC to quantify the effect of farnesylation on the temperature-triggered phase separation of elastin-based proteins.…”

“…Biopolymers with programmable thermoresponse (such as ELPs) are attractive materials for biomedical applications because the temperature can be increased locally as a therapeutic modality while causing minimal damage to healthy tissues . While the effect of amino acid mutations on the liquid–liquid phase separation of proteins is under intense investigation, , our understanding of the effect of lipidation on the phase-boundaries remains incomplete.…”

Lipidation Alters the Structure and Hydration of Myristoylated Intrinsically Disordered Proteins

“…Utilization of PTMs offers a promising direction for the construction of hybrid protein materials with diversified physicochemical properties, expanded engineering capabilities, and/or altered biological behavior. − For instance, lipidation of stimuli-responsive intrinsically disordered proteins (IDPs) has been used to combine the hierarchical assembly of lipids with the temperature-responsiveness of IDPs to create assemblies whose nano- and mesoscale structure can change with temperature. − Specifically, fatty-acid-modified elastin-like polypeptides (FAMEs) can form a diverse palette of spherical and anisotropic structures as a function of temperature including spherical nanoparticles ,, that can change size or transition into nanoworms or fibers . The ability to reprogram the nanoassembly of these hybrid biomaterials as a function of temperature is desirable for biomedical applications, including drug delivery. , Because temperature can be easily and precisely modulated as a therapeutic modality, this thermoresponsiveness can be harnessed to regulate the transport and localization of carriers and encapsulated drugs while causing minimal damage to healthy tissues …”