Liquefaction of Biopolymers: Solvent-free Liquids and Liquid Crystals from Nucleic Acids and Proteins

Abstract

ConspectusBiomacromolecules, such as nucleic acids, proteins, and virus particles, are persistent molecular entities with dimensions that exceed the range of their intermolecular forces hence undergoing degradation by thermally induced bond-scission upon heating. Consequently, for this type of molecule, the absence of a liquid phase can be regarded as a general phenomenon. However, certain advantageous properties usually associated with the liquid state of matter, such as processability, flowability, or molecular mobility, are highly sought-after features for biomacromolecules in a solvent-free environment. Here, we provide an overview over the design principles and synthetic pathways to obtain solvent-free liquids of biomacromolecular architectures approaching the topic from our own perspective of research. We will highlight the milestones in synthesis, including a recently developed general surfactant complexation method applicable to a large variety of biomacromolecules as well as other synthetic principles granting access to electrostatically complexed proteins and DNA.These synthetic pathways retain the function and structure of the biomacromolecules even under extreme, nonphysiological conditions at high temperatures in water-free melts challenging the existing paradigm on the role of hydration in structural biology. Under these conditions, the resulting complexes reveal their true potential for previously unthinkable applications. Moreover, these protocols open a pathway toward the assembly of anisotropic architectures, enabling the formation of solvent-free biomacromolecular thermotropic liquid crystals. These ordered biomaterials exhibit vastly different mechanical properties when compared to the individual building blocks. Beyond the preparative aspects, we will shine light on the unique potential applications and technologies resulting from solvent-free biomacromolecular fluids: From charge transport in dehydrated liquids to DNA electrochromism to biocatalysis in the absence of a protein hydration shell. Moreover, solvent-free biological liquids containing viruses can be used as novel storage and process media serving as a formulation technology for the delivery of highly concentrated bioactive compounds. We are confident that this new class of hybrid biomaterials will fuel further studies and applications of biomacromolecules beyond water and other solvents and in a much broader context than just the traditional physiological conditions.

Extracellular Matrix Proteins Involved in Alzheimer's Disease

“…(VPGVG) n ELPs showed typical thermal‐related phase‐transition behavior. Soluble forms of ELPs can be triggered to become hydrophobic proteinaceous aggregates upon heating over the transitional point ( T t ; Figure A and B) . Furthermore, it was found that ELP90 induced the overproduction of Aβ peptides in AD model cells under physiological conditions (37 °C).…”

“…[38,39] (VPGVG) n ELPs showed typical thermal-related phase-transition behavior.Soluble forms of ELPs can be triggered to become hydrophobic proteinaceous aggregates upon heatingo vert he transitional point (T t ;F igure3Aa nd B). [40,41] Furthermore, it was found that ELP90 induced the overproduction of Ab peptides in AD model cells under physiological conditions (37 8C). Treatment with ELP90 in mice resulted in both AD-related pathological and neurobehavioral phenotypes, including upregulation of the Ab level and cognitive impairments( Figure 3C).…”

Designing Liquid‐Infused Surfaces for Medical Applications: A Review

“…Recent work has shown how liquid crystal surfaces and shapes can be highly sensitive to low concentrations of toxins, as well as how their ordering properties control and respond to bacterial mobility . In addition, liquids composed of solvent‐free proteins have been designed to retain gas‐binding and catalytic functions . Synergy between these liquids' responsive properties and the mechanical and chemical forces imposed on them by the underlying microstructure holds possibilities for generating an even greater diversity of responses, enabling the composite surfaces to be designed for finer discrimination and sensitivity.…”

Supercharged Proteins and Polypeptides

“…In synthetic vinyl polymers or polypeptides synthesized by ring opening polymerization, positioning of cationic monomers is much harder to achieve when combined with neutral monomers . Moreover, SUPs can be complexed with other charged molecules to obtain new properties . Especially, this holds true for combining SUPs with oppositely charged surfactants to form charge stoichiometric complexes.…”