Stronger than Steel, Tougher than Kevlar

Spider silk is said to be one of the strongest, toughest materials on the Earth. Now engineers at Washington University in St. Louis have designed amyloid silk hybrid proteins and produced them in engineered bacteria. The resulting fibers are stronger and tougher than some natural spider silks.

To be precise, the artificial silk — dubbed “polymeric amyloid” fiber — was not technically produced by researchers, but by bacteria that were genetically engineered in the lab of Fuzhong Zhang, a professor in the Department of Energy, Environmental & Chemical Engineering in the McKelvey School of Engineering.

Zhang has worked with spider silk before. In 2018, his lab engineered bacteria that produced a recombinant spider silk with performance on par with its natural counterparts in all of the important mechanical properties.

After our previous work, I wondered if we could create something better than spider silk using our synthetic biology platform,” Zhang said.

The research team, which includes first author Jingyao Li, a PhD student in Zhang’s lab, modified the amino acid sequence of spider silk proteins to introduce new properties, while keeping some of the attractive features of spider silk.

A problem associated with recombinant spider silk fiber — without significant modification from natural spider silk sequence — is the need to create β-nanocrystals, a main component of natural spider silk, which contributes to its strength. “Spiders have figured out how to spin fibers with a desirable amount of nanocrystals,” Zhang said. “But when humans use artificial spinning processes, the amount of nanocrystals in a synthetic silk fiber is often lower than its natural counterpart.

Their research was published in the journal ACS Nano.


New Theory To Prevent Alzheimer’s

Alzheimer’s disease, the most common cause of dementia among the elderly, is characterized by plaques and tangles in the brain, with most efforts at finding a cure focused on these abnormal structures. But a University of California, Riverside, research team has identified alternate chemistry that could account for the various pathologies associated with the diseasePlaques and tangles have so far been the focus of attention in this progressive disease that currently afflicts more than 5.5 million people in the United States. Plaques, deposits of a protein fragment called beta-amyloid, look like clumps in the spaces between neurons. Tangles, twisted fibers of tau, another protein, look like bundles of fibers that build up inside cells.

The dominant theory based on beta-amyloid buildup has been around for decades, and dozens of clinical trials based on that theory have been attempted, but all have failed,” said Ryan R. Julian, a professor of chemistry who led the research team. “In addition to plaques, lysosomal storage is observed in brains of people who have Alzheimer’s disease. Neurons — fragile cells that do not undergo cell division — are susceptible to lysosomal problems, specifically, lysosomal storage, which we report is a likely cause of Alzheimer’s disease.”

An organelle within the cell, the lysosome serves as the cell’s trashcan. Old proteins and lipids get sent to the lysosome to be broken down to their building blocks, which are then shipped back out to the cell to be built into new proteins and lipids. To maintain functionality, the synthesis of proteins is balanced by the degradation of proteins.

The lysosome, however, has a weakness: If what enters does not get broken down into little pieces, then those pieces also can’t leave the lysosome. The cell decides the lysosome is not working and “stores it, meaning the cell pushes the lysosome to the side and proceeds to make a new one. If the new lysosome also fails, the process is repeated, resulting in lysosome storage.

The brains of people who have lysosomal storage disorder, another well-studied disease, and the brains of people who have Alzheimer’s disease are similar in terms of lysosomal storage,” Julian said. “But lysosomal storage disorder symptoms show up within a few weeks after birth and are often fatal within a couple of years. Alzheimer’s disease occurs much later in life. The time frames are, therefore, very different.”

Julian’s collaborative team of researchers in the Department of Chemistry and the Division of Biomedical Sciences at UC Riverside posits that long-lived proteins, including beta-amyloid and tau, can undergo spontaneous modifications that can make them undigestible by the lysosomes. “Long-lived proteins become more problematic as we age and could account for the lysosomal storage seen in Alzheimer’s, an age-related disease,” Julian said. “If we are correct, it would open up new avenues for treatment and prevention of this disease.”

Study results appear in ACS Central Science, a journal of the American Chemical Society.