A Multifunctional Cosolvent Pair Reveals Molecular Principles of Biomass Deconstruction.

The complex structure of plant cell walls resists chemical or biological degradation, challenging the breakdown of lignocellulosic biomass into renewable chemical precursors that could form the basis of future production of green chemicals and transportation fuels. Here, experimental and computational results reveal that the effect of the tetrahydrofuran (THF)-water cosolvents on the structure of lignin and on its interactions with cellulose in the cell wall drives multiple synergistic mechanisms leading to the efficient breakdown and fractionation of biomass into valuable chemical precursors. Molecular simulations show that THF-water is an excellent "theta" solvent, such that lignin dissociates from itself and from cellulose and expands to form a random coil. The expansion of the lignin molecules exposes interunit linkages, rendering them more susceptible to depolymerization by acid-catalyzed cleavage of aryl-ether bonds. Nanoscale infrared sensors confirm cosolvent-mediated molecular rearrangement of lignin in the cell wall of micrometer-thick hardwood slices and track the disappearance of lignin. At bulk scale, adding dilute acid to the cosolvent mixture liberates the majority of the hemicellulose and lignin from biomass, allowing unfettered access of cellulolytic enzymes to the remaining cellulose-rich material, allowing them to sustain high rates of hydrolysis to glucose without enzyme deactivation. Through this multiscale analysis, synergistic mechanisms for biomass deconstruction are identified, portending a paradigm shift toward first-principles design and evaluation of other cosolvent methods to realize low cost fuels and bioproducts.

Unmodified and pyroglutamylated amyloid ß peptides form hypertoxic hetero-oligomers of unique secondary structure.

Amyloid ß (Aß) peptide plays a major role in Alzheimer's disease (AD) and occurs in multiple forms, including pyroglutamylated Aß (AßpE). Identification and characterization of the most cytotoxic Aß species is necessary for advancement in AD diagnostics and therapeutics. While in brain tissue multiple Aß species act in combination, structure/toxicity studies and immunotherapy trials have been focused on individual forms of Aß. As a result, the molecular composition and the structural features of "toxic Aß oligomers" have remained unresolved. Here, we have used a novel approach, hydration from gas phase coupled with isotope-edited Fourier transform infrared (FTIR) spectroscopy, to identify the prefibrillar assemblies formed by Aß and AßpE and to resolve the structures of both peptides in combination. The peptides form unusual ß-sheet oligomers stabilized by intramolecular H-bonding as opposed to intermolecular H-bonding in the fibrils. Time-dependent morphological changes in peptide assemblies have been visualized by atomic force microscopy. Aß/AßpE hetero-oligomers exert unsurpassed cytotoxic effect on PC12 cells as compared to oligomers of individual peptides or fibrils. These findings lead to a novel concept that Aß/AßpE hetero-oligomers, not just Aß or AßpE oligomers, constitute the main neurotoxic conformation. The hetero-oligomers thus present a new biomarker that may be targeted for development of more efficient diagnostic and immunotherapeutic strategies to combat AD.