Genetically encoded lipid–polypeptide hybrid biomaterials that exhibit temperature-triggered hierarchical self-assembly

Fetahaj

et al. 2019

Chemistry A European J

131

157

Liquid–liquid phase separation (LLPS) of proteins and other biomolecules play a critical role in the organization of extracellular materials and membrane‐less compartmentalization of intra‐organismal spaces through the formation of condensates. Structural properties of such mesoscopic droplet‐like states were studied by spectroscopy, microscopy, and other biophysical techniques. The temperature dependence of biomolecular LLPS has been studied extensively, indicating that phase‐separated condensed states of proteins can be stabilized or destabilized by increasing temperature. In contrast, the physical and biological significance of hydrostatic pressure on LLPS is less appreciated. Summarized here are recent investigations of protein LLPS under pressures up to the kbar‐regime. Strikingly, for the cases studied thus far, LLPSs of both globular proteins and intrinsically disordered proteins/regions are typically more sensitive to pressure than the folding of proteins, suggesting that organisms inhabiting the deep sea and sub‐seafloor sediments, under pressures up to 1 kbar and beyond, have to mitigate this pressure‐sensitivity to avoid unwanted destabilization of their functional biomolecular condensates. Interestingly, we found that trimethylamine‐N‐oxide (TMAO), an osmolyte upregulated in deep‐sea fish, can significantly stabilize protein droplets under pressure, pointing to another adaptive advantage for increased TMAO concentrations in deep‐sea organisms besides the osmolyte's stabilizing effect against protein unfolding. As life on Earth might have originated in the deep sea, pressure‐dependent LLPS is pertinent to questions regarding prebiotic proto‐cells. Herein, we offer a conceptual framework for rationalizing the recent experimental findings and present an outline of the basic thermodynamics of temperature‐, pressure‐, and osmolyte‐dependent LLPS as well as a molecular‐level statistical mechanics picture in terms of solvent‐mediated interactions and void volumes.

Section: Discussionmentioning

confidence: 99%

Temperature, Hydrostatic Pressure, and Osmolyte Effects on Liquid–Liquid Phase Separation in Protein Condensates: Physical Chemistry and Biological Implications

Fetahaj

et al. 2019

Chemistry A European J

131

157

Section: Elp‐hybrid Self‐assembliesmentioning

confidence: 99%

Engineering the Architecture of Elastin‐Like Polypeptides: From Unimers to Hierarchical Self‐Assembly

Saha

Banskota

Roberts

et al. 2020

Advanced Therapeutics

Self Cite

Well‐defined tunable nanostructures formed through the hierarchical self‐assembly of peptide building blocks have drawn significant attention due to their potential applications in biomedical science. Artificial protein polymers derived from elastin‐like polypeptides (ELPs), which are based on the repeating sequence of tropoelastin (the water‐soluble precursor to elastin), provide a promising platform for creating nanostructures due to their biocompatibility, ease of synthesis, and customizable architecture. By designing the sequence and composition of ELPs at the gene level, their physicochemical properties can be controlled to a degree that is unmatched by synthetic polymers. A variety of ELP‐based nanostructures are designed, inspired by the self‐assembly of elastin and other proteins in biological systems. The choice of building blocks determines not only the physical properties of the nanostructures, but also their self‐assembly into architectures ranging from spherical micelles to elongated nanofibers. This review focuses on the molecular determinants of ELP and ELP‐hybrid self‐assembly and formation of spherical, rod‐like, worm‐like, fibrillar, and vesicle architectures. A brief discussion of the potential biomedical applications of these supramolecular assemblies is also included.

“…The incorporation of ELRs into the composite hydrogels can be used to improve the mechanical properties of the network as well as provide a broad range of bioactive cues that promote cell adhesion and proliferation. [274][275][276][277][278][279] For instance, the combination of collagen with ELRs enables the production of biofunctional hydrogels with tunable mechanical properties for the regeneration of bone and soft tissues injuries, or for the manufacture of vascular grafts. [280][281][282][283][284] Indeed, it has been demonstrated that the osteoinductive activity of collagen can be synergistically combined with the mechanical properties of the ELRs to biofabricate 3D polymeric networks to guide tissue regeneration.…”

Section: Hybrid Elr-based Scaffoldsmentioning

confidence: 99%

Elastin‐Like Recombinamers: Deconstructing and Recapitulating the Functionality of Extracellular Matrix Proteins Using Recombinant Protein Polymers

Acosta

Quintanilla‐Sierra

Mbundi

et al. 2020

Adv Funct Materials

In the development of tissue engineering strategies to replace, remodel, regenerate, or support damaged tissue, the development of bioinspired biomaterials that recapitulate the physicochemical characteristics of the extracellular matrix has received increased attention. Given the compositional heterogeneity and tissue-to-tissue variation of the extracellular matrix, the design, choice of polymer, crosslinking, and nature of the resulting biomaterials are normally depended on intended application. Generally, these biomaterials are usually made of degradable or nondegradable biomaterials that can be used as cell or drug carriers. In recent years, efforts to endow reciprocal biomaterial-cell interaction properties in scaffolds have inspired controlled synthesis, derivatization, and functionalization of the polymers used. In this regard, elastin-like recombinant proteins have generated interest and continue to be developed further owing to their modular design at a molecular level. In this review, the authors provide a summary of key extracellular matrix features relevant to biomaterials design and discuss current approaches in the development of extracellular matrix-inspired elastin-like recombinant protein based biomaterials.