Macromolecular Phase Transitions in Human Physiology and Pathology

Dear Colleagues,

Biomolecular phase transitions have been recently identified as a key mechanism of subcellular organization. Phase transitions allow for the dynamic formation-dissolution of cellular, membraneless organelles such as cytosolic stress granules, P-bodies, and germ granules; and nuclear Cajal bodies, paraspeckles, nuclear speckles, PML-bodies, and nucleolus. Phase transitions also facilitate several biomolecular assembly processes including chromatin condensation, transcription bubble formation, RNA-induced silencing complex formation, and signalling complex assembly.  Thus, it is becoming increasingly clear that the biomolecular phase transitions play prominent roles in the spatiotemporal regulation of cellular functions.

In vitro studies suggest that many disordered proteins undergo phase transitions at physiologic protein concentrations. Protein phase transitions can result in the formation of liquid-like condensates or solid-like fibrillar aggregates. For many proteins, liquid condensates can eventually transform to solid fibrils. Such liquid-to-solid phase transitions are exacerbated by disease-linked mutations and are assumed to represent protein pathologic transformation. Many biochemical perturbations such as post-translational modifications, ligand interactions, and RNA enrichment/depletion tune liquid-to-solid phase transitions of protein-rich membraneless organelles both in vitro and in vivo. Interestingly, recent reports indicate that disease-associated RNAs (linked to nucleic acid repeat-expansion disorders) themselves can undergo liquid–liquid phase transitions to form RNA condensates/gels.

This Special Issue of Biomolecules is focused on understanding the role of phase transitions in a multitude of human pathologies. We encourage the submission of original research articles or communications that contribute to the molecular-level as well as a mesoscopic-level understanding of biomolecule condensation, protein fibrillation, and macromolecule condensation-linked aggregation in the context of both human physiology and pathology.  Critical reviews that synthesize the current research literature on biomolecular phase transitions and provide guidance for newcomers on emerging directions are also highly welcome.

Prof. Dr. Josephine C. Ferreon
Prof. Dr. Rajan Lamichhane
Prof. Dr. Allan Chris M. Ferreon
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• Liquid–liquid phase separation
• Protein fibrillation
• Intrinsically disordered proteins
• Nucleic acid binding proteins
• Protein–protein interaction
• RNA-protein interaction
• Post-translational modifications
• Macromolecular assembly
• Folding and misfolding of biomolecules
• Ribonucleoproteins.