Protein molecules have the ability to form a rich variety of natural and artificial structures and materials. We show that amyloid fibrils, ordered supramolecular nanostructures that are self-assembled from a wide range of polypeptide molecules, have rigidities varying over four orders of magnitude, and constitute a class of high-performance biomaterials. We elucidate the molecular origin of fibril material properties and show that the major contribution to their rigidity stems from a generic interbackbone hydrogen-bonding network that is modulated by variable side-chain interactions.

https://science.sciencemag.org/content/sci/318/5858/1900.full.pdf

Role of intermolecular forces in defining material properties of protein nanofibrils.

Amyloid or amyloid-like fibrils represent a general class of nanomaterials that can be formed from many different peptides and proteins. Although these structures have an important role in neurodegenerative disorders, amyloid materials have also been exploited for functional purposes by organisms ranging from bacteria to mammals. Here we review the functional and pathological roles of amyloid materials and discuss how they can be linked back to their nanoscale origins in the structure and nanomechanics of these materials. We focus on insights both from experiments and simulations, and discuss how comparisons between functional protein filaments and structures that are assembled abnormally can shed light on the fundamental material selection criteria that lead to evolutionary bias in multiscale material design in nature.

/pdf/nanomechanics-of-functional-and-pathological-amyloid-403flt6xr9.pdf

Nanomechanics of functional and pathological amyloid materials

We report the detailed mechanical characterization of individual amyloid fibrils by atomic force microscopy and spectroscopy These self-assembling materials, formed here from the protein insulin, were shown to have a strength of 06 ± 04 GPa, comparable to that of steel (06–18 GPa), and a mechanical stiffness, as measured by Young's modulus, of 33 ± 04 GPa, comparable to that of silk (1–10 GPa) The values of these parameters reveal that the fibrils possess properties that make these structures highly attractive for future technological applications In addition, analysis of the solution-state growth kinetics indicated a breakage rate constant of 17 ± 13 × 10−8 s−1, which reveals that a fibril 10 μm in length breaks spontaneously on average every 47 min, suggesting that internal fracturing is likely to be of fundamental importance in the proliferation of amyloid fibrils and therefore for understanding the progression of their associated pathogenic disorders

https://www.pnas.org/content/pnas/103/43/15806.full.pdf

Characterization of the nanoscale properties of individual amyloid fibrils.

The aggregation of proteins is of fundamental relevance in a number of daily phenomena, as important and diverse as blood coagulation, medical diseases, or cooking an egg in the kitchen. Colloidal food systems, in particular, are examples that have great significance for protein aggregation, not only for their importance and implications, which touches on everyday life, but also because they allow the limits of the colloidal science analogy to be tested in a much broader window of conditions, such as pH, ionic strength, concentration and temperature. Thus, studying the aggregation and self-assembly of proteins in foods challenges our understanding of these complex systems from both the molecular and statistical physics perspectives. Last but not least, food offers a unique playground to study the aggregation of proteins in three, two and one dimensions, that is to say, in the bulk, at air/water and oil/water interfaces and in protein fibrillation phenomena. In this review we will tackle this very ambitious task in order to discuss the current understanding of protein aggregation in the framework of foods, which is possibly one of the broadest contexts, yet is of tremendous daily relevance.

http://iopscience.iop.org/article/10.1088/0034-4885/76/4/046601/pdf

The self-assembly, aggregation and phase transitions of food protein systems in one, two and three dimensions

Cellular structures are shaped by hydrogen and ionic bonds, plus van der Waals and hydrophobic forces. In cells crowded with macromolecules, a little-known and distinct force—the “depletion attraction”—also acts. We review evidence that this force assists in the assembly of a wide range of cellular structures, ranging from the cytoskeleton to chromatin loops and whole chromosomes.

https://rupress.org/jcb/article-pdf/175/5/681/1328201/jcb_200609066.pdf

The depletion attraction: an underappreciated force driving cellular organization

Micromechanics of isolated sickle cell hemoglobin fibers: bending moduli and persistence lengths.

https://homepages.warwick.ac.uk/~phscz/research/publications/twistJMB.pdf

Anisotropy in sickle hemoglobin fibers from variations in bending and twist.

We report on observations of “zippering” that occurs when two sickle hemoglobin fibers come together side by side. A transient Y-shaped object is formed which “zips” closed. We have been able to show how the strength of the interactions that drive this may be estimated by studying the frustrated structures sometimes formed between several fibers. Our measurements, when combined with mechanical constants determined by an analysis of bending fluctuations, allow us to make the first estimate of the magnitude of these interactions, of the order of 7kBT
μm−1. Hemoglobin volume fractions of tens of % lead to significant depletion forces. We estimate the magnitude of both the depletion and Van der Waals forces between pairs of single fibers. We study how these are effected by the helical nature of the fibers and renormalised by bending fluctuations, calculations that could have wider applications beyond sickle hemoglobin fibers. Our theoretical analysis of single fibers is in encouraging, although not fully quantitative, agreement with our measurements. We conclude that the physics and rheology of the hemoglobin gel, as well as the pathology of sickle cell anemia itself, may be influenced by depletion interactions.

Jiang Cheng Wang

Papers

Micromechanics of isolated sickle cell hemoglobin fibers: bending moduli and persistence lengths.

Anisotropy in sickle hemoglobin fibers from variations in bending and twist.

Interactions between sickle hemoglobin fibers

Sickle hemoglobin fibers: mechanisms of depolymerization.

Measuring forces between protein fibers by microscopy