A generic statistical mechanical model is presented for the self-assembly of chiral rod-like units, such as beta-sheet-forming peptides, into helical tapes, which with increasing concentration associate into twisted ribbons (double tapes), fibrils (twisted stacks of ribbons), and fibers (entwined fibrils). The finite fibril width and helicity is shown to stem from a competition between the free energy gain from attraction between ribbons and the penalty because of elastic distortion of the intrinsically twisted ribbons on incorporation into a growing fibril. Fibers are stabilized similarly. The behavior of two rationally designed 11-aa residue peptides, P(11)-I and P(11)-II, is illustrative of the proposed scheme. P(11)-I and P(11)-II are designed to adopt the beta-strand conformation and to self-assemble in one dimension to form antiparallel beta-sheet tapes, ribbons, fibrils, and fibers in well-defined solution conditions. The energetic parameters governing self-assembly have been estimated from the experimental data using the model. The 8-nm-wide fibrils consist of eight tapes, are extremely robust (scission energy approximately 200 k(B)T), and sufficiently rigid (persistence length l(fibril) approximately 20-70 microm) to form nematic solutions at peptide concentration c approximately 0.9 mM (volume fraction approximately 0.0009 vol/vol), which convert to self-supporting nematic gels at c > 4 mM. More generally, these observations provide a new insight into the generic self-assembling properties of beta-sheet-forming peptides and shed new light on the factors governing the structures and stability of pathological amyloid fibrils in vivo. The model also provides a prescription of routes to novel macromolecules based on a variety of self-assembling chiral units, and protocols for extraction of the associated energy changes.

https://www.pnas.org/content/pnas/98/21/11857.full.pdf

Hierarchical self-assembly of chiral rod-like molecules as a model for peptide β-sheet tapes, ribbons, fibrils, and fibers

Imagine a world in which any protein, either naturally occurring or designed by man, could be produced safely, inexpensively and in almost unlimited quantities using only simple nutrients, water and sunlight. This could one day become reality as we learn to harness the power of plants for the production of recombinant proteins on an agricultural scale. Molecular farming in plants has already proven to be a successful way of producing a range of technical proteins. The first plant-derived recombinant pharmaceutical proteins are now approaching commercial approval, and many more are expected to follow.

/pdf/the-production-of-recombinant-pharmaceutical-proteins-in-h5b4asi42c.pdf

The production of recombinant pharmaceutical proteins in plants.

Plants and human health in the twenty-first century

Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(03)00279-8.pdf

Molecular farming in plants: host systems and expression technology.

Potato tubers have been successfully used for high-level production of a recombinant single-chain Fv (ScFv) antibody. Ubiquitous high-level expression was achieved under control of the CaMV 35S promoter through retention of the scFv protein in the endoplasmic reticulum. Recombinant antibodies accumulated up to 2% of total soluble tuber protein. After 1.5 years of tuber storage at 4 °C still half of the amount of scFv present in freshly harvested tubers was detectable. Its specific activity did not decrease during tuber storage. Recombinant protein could be efficiently purified from crude extracts by affinity chromatography.

Barbara Kettig

Papers

Potato tubers as a biofactory for recombinant antibodies