No abstract

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

The biological effects of magnetic fields (MFs) have been a controversial issue. Fortunately, in recent years, there has been increasing evidence that MFs do affect biological systems. However, the physical mechanism remains unclear. Here, we show that MFs (16 T) reduce apoptosis in cell lines by inhibiting liquid–liquid phase separation (LLPS) of Tau-441, suggesting that the MF effect on LLPS may be one of the mechanisms for understanding the “mysterious” magnetobiological effects. The LLPS of Tau-441 occurred in the cytoplasm after induction with arsenite. The phase-separated droplets of Tau-441 recruited hexokinase (HK), resulting in a decrease in the amount of free HK in the cytoplasm. In cells, HK and Bax compete to bind to the voltage-dependent anion channel (VDAC I) on the mitochondrial membrane. A decrease in the number of free HK molecules increased the chance of Bax binding to VDAC I, leading to increased Bax-mediated apoptosis. In the presence of a static MF, LLPS was marked inhibited and HK recruitment was reduced, resulting in an increased probability of HK binding to VDAC I and a decreased probability of Bax binding to VDAC I, thus reducing Bax-mediated apoptosis. Our findings revealed a new physical mechanism for understanding magnetobiological effects from the perspective of LLPS. In addition, these results show the potential applications of physical environments, such as MFs in this study, in the treatment of LLPS-related diseases.

The abnormal accumulation of fused in sarcoma (FUS) is a pathological hallmark in a proportion of patients with frontotemporal dementia and amyotrophic lateral sclerosis.

Liquid-liquid phase separation (LLPS) is a ubiquitous process found in a variety of fields. It is of particular importance in biological sciences since it plays essential and vital roles in a number of physiological and pathological processes in biological systems. After LLPS, the dense droplets can grow in size via incorporating solutes from surrounding environment and in some cases coalescing with other droplets. Interestingly, the size of the dense droplets seems to have an upper limit but the mechanism remains to be explored. Since the droplet size can be essential for biological functioning, it is important to understand the size evolution of the phase separated droplets. Here we propose a physical mechanism with consideration of impurities on the surface of the dense liquid droplets. The theoretical predictions can be used to explain the observations on the size evolution. Based on the coalescence mechanism, we succeeded for the first time performing a challenging task, i.e., growing a single suspended protein crystal via merging phase-separated droplets in a fully non-contact manner. The mechanism observed may be considered as a basic model for researches in much broader fields involving phase separation, such as in biology, materials science, physics, chemistry, and meteorology.