Biomolecular Phase Transitions and the Mechanochemical Control of Cells in Health & Disease

Recent research has elucidated the biological importance of phase transitions in, and phase separation of, biological macromolecules.  These biophysical processes provide fundamental routes to the self-assembly of many key structures in living organisms.  Both liquid-liquid and liquid-solid phase separation can be involved, as can both healthy (normative) and diseased (non-normative) biological states. Work to understand how these phase changes occur and what controls them has drawn on contributions from physicists, material scientists, cellular and molecular biologists, data scientists, bioengineers, and physicians. As a result of this multidisciplinary field of work, emerging knowledge points to integrated mechanochemical operation and control in healthy cells that arises from the interplay between mesoscopic condensate phase formation, microrheology, and mechanosensation. In contrast, highly-concentrated dense liquid phases of protein, which are very close to condensation and precipitation in healthy cells, can form solid phases tightly linked to the causes of disease that are neurodegenerative, such as Parkinson’s, Alzheimer’s, and Amyotrophic Lateral Sclerosis, and circulatory, such as Sickle Cell Disease. This new knowledge points the way to controlling protein phase transitions as a way of treating diseases, and new medicines are already under development to do exactly this.

The goal of this Special Issue of Biophysics Reviews is to bring together the diverse group of scientists, engineers and physicians who are doing fundamental work on the biology and physics of phase transitions and phase separation and those who are applying biophysical understanding of phase behavior to create new approaches to promoting health.  Work along wide ranges of size and time scales, the fundamental-applied continuum, and the health-disease axis will all be welcomed.