It is possible to tailor the frequency of laser light to selectively disrupt the bonds or structure of particular arrangements of molecules – such as, say, the harmful protein aggregates found in neurodegenerative and other age-related conditions. Researchers here showcase early work into the disruption of amyloids, a class of altered of proteins that feature prominently in numerous conditions. The challenge in this sort of approach is usually not that of achieving the desired disruption, but rather doing so without the delivery of so much energy, released as heat, that the process kills surrounding cells and tissues. Past early stage efforts have floundered on that problem.

A notable characteristic of several neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, is the formation of harmful plaques that contain aggregates – also known as fibrils – of amyloid proteins. Unfortunately, even after decades of research, getting rid of these plaques has remained a herculean challenge. Thus, the treatment options available to patients with these disorders are limited and not very effective.

In recent years, instead of going down the chemical route using drugs, some scientists have turned to alternative approaches, such as ultrasound, to destroy amyloid fibrils and halt the progression of Alzheimer’s disease. Now, a research team has used novel methods to show how infrared-laser irradiation can destroy amyloid fibrils. While laser experiments coupled with various microscopy methods can provide information about the morphology and structural evolution of amyloid fibrils after laser irradiation, these experiments have limited spatial and temporal resolutions, thus preventing a full understanding of the underlying molecular mechanisms. On the other hand, though this information can be obtained from molecular simulations, the laser intensity and irradiation time used in simulations are very different from those used in actual experiments. It is therefore important to determine whether the process of laser-induced fibril dissociation obtained through experiments and simulations is similar.”

The scientists used a portion of a yeast protein that is known to form amyloid fibrils on its own. In their laser experiments, they tuned the frequency of an infrared laser beam to that of the “amide I band” of the fibril, creating resonance. Scanning electron microscopy images confirmed that the amyloid fibrils disassembled upon laser irradiation at the resonance frequency, and a combination of spectroscopy techniques revealed details about the final structure after fibril dissociation. For the simulations, the researchers employed a technique that a few members of the current team had previously developed, called “nonequilibrium molecular dynamics (NEMD) simulations.” Its results corroborated those of the experiment and additionally clarified the entire amyloid dissociation process down to very specific details. Through the simulations, the scientists observed that the process begins at the core of the fibril where the resonance breaks intermolecular hydrogen bonds and thus separates the proteins in the aggregate. The disruption to this structure then spreads outward to the extremities of the fibril.