Poster V1 - The Electrochemical Functions of Biomolecular Condensates

Introduction: Biomolecular condensates, formed through associative or segregative transition of biomacromolecules, are ubiquitous subcellular structures that regulate diverse cellular functions. However, their fundamental physicochemical features and functions are largely unknown. Our lab works on uncovering the physical chemistry and resulting electrochemical functions of biomolecular condensates. In this talk, I will discuss the molecular principles underlying the fundamental physicochemical features of biomolecular condensates, such as pH gradient and interfacial electric field. I will then introduce recently uncovered physicochemical and electrochemical functions of biomolecular condensates. Lastly, I will use some examples to showcase how these fundamental features can be used for understanding biological functions and designing biology.

Materials and

Methods: We designed and engineered intrinsically disordered proteins (IDPs) with distinct phase transition properties to engineer biomolecular condensates. The designed condensates were used to explore the physicochemical functions of biomolecular condensates and construct sequence-property-function relationship. We implemented coarse-grained simulation, confocal microscopy, electrochemical potentiometry, mass spectroscopy and chemical assays to define and characterize the fundamental features and functions of condensates.

Results, Conclusions, and Discussions: Our work discovered a previously unknown functioning mechanism of biomolecular condensates, which goes beyond the biomolecular functions encoded in the biomolecules participating in condensate formation. This discovery sheds light on how condensates can be critical to cellular chemical homeostasis and establishes new fundamental capabilities for synthetic biology and molecular engineering.

Acknowledgements (Optional): We acknowledge the support and discussion from Prof. Ashutosh Chilkoti and Prof. Lingchong You of Duke University, and Prof. Richard N. Zare of Stanford University. We thank the kind experimental supports from the group of Prof. Rohit V. Pappu and the Center for Biomolecular condensates of Washington University.

References: 1. Dai. et al. Nature chemical biology 19 (4), 518-528
2. Dai. et al. Chem 9 (6), 1594-1609
3. Dai. et al. Nature Reviews Bioengineering 1 (7), 466-480