The study of protein aggregation, and amyloidosis in particular, has gained considerable interest in recent times. Several neurodegenerative diseases, such as Alzheimer’s (AD) and Parkinson’s (PD) show a characteristic buildup of proteinaceous aggregates in several organs, especially the brain. Despite the enormous upsurge in research articles in this arena, it would not be incorrect to say that we still lack a crystal-clear idea surrounding these notorious aggregates. In this review, we attempt to present a holistic picture on protein aggregation and amyloids in particular. Using a chronological order of discoveries, we present the case of amyloids right from the onset of their discovery, various biophysical techniques, including analysis of the structure, the mechanisms and kinetics of the formation of amyloids. We have discussed important questions on whether aggregation and amyloidosis are restricted to a subset of specific proteins or more broadly influenced by the biophysiochemical and cellular environment. The therapeutic strategies and the significant failure rate of drugs in clinical trials pertaining to these neurodegenerative diseases have been also discussed at length. At a time when the COVID-19 pandemic has hit the globe hard, the review also discusses the plausibility of the far-reaching consequences posed by the virus, such as triggering early onset of amyloidosis. Finally, the application(s) of amyloids as useful biomaterials has also been discussed briefly in this review.

The mechanical properties, or mechanotypes, of cells are largely determined by their deformability and contractility. The ability of cancer cells to deform and generate contractile force is critical in multiple steps of metastasis. Identifying soluble cues that regulate cancer cell mechanotypes and understanding the underlying molecular mechanisms regulating these cellular mechanotypes could provide novel therapeutic targets to prevent metastasis. Although a strong correlation between high glucose level and cancer metastasis has been demonstrated, the causality is not elucidated, and the underlying molecular mechanisms remain largely unknown. In this study, using novel high-throughput mechanotyping assays, we show that human breast cancer cells become less deformable and more contractile with increased extracellular glucose levels (>5 mM). These altered cell mechanotypes are due to increased F-actin rearrangement and non-muscle myosin II (NMII) activity. We identify the cAMP-RhoA-ROCK-NMII axis to play a major role in regulating cell mechanotypes at high extracellular glucose levels, whereas calcium and myosin light chain kinase (MLCK) are not required. The altered mechanotypes are also associated with increased cell migration and invasion. Our study identifies key components in breast cancer cells that convert high extracellular glucose levels into changes in cellular mechanotype and behaviors relevant in cancer metastasis.