Biomolecular condensate phase diagrams with a combinatorial microdroplet platform

William E. Arter, Runzhang Qi, Nadia A. Erkamp, Georg Krainer, Kieran Didi, Timothy J. Welsh, Julia Acker, Jonathan Nixon-Abell, Seema Qamar, Jordina Guillén-Boixet, Titus M. Franzmann, David Kuster, Anthony A. Hyman, Alexander Borodavka, Peter St George-Hyslop, Simon Alberti and Tuomas P. J. Knowles ()
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William E. Arter: University of Cambridge
Runzhang Qi: University of Cambridge
Nadia A. Erkamp: University of Cambridge
Georg Krainer: University of Cambridge
Kieran Didi: University of Cambridge
Timothy J. Welsh: University of Cambridge
Julia Acker: University of Cambridge
Jonathan Nixon-Abell: University of Cambridge
Seema Qamar: University of Cambridge
Jordina Guillén-Boixet: Technische Universität Dresden
Titus M. Franzmann: Technische Universität Dresden
David Kuster: Max Planck Institute for Molecular Cell Biology and Genetics
Anthony A. Hyman: Max Planck Institute for Molecular Cell Biology and Genetics
Alexander Borodavka: University of Cambridge
Peter St George-Hyslop: University of Cambridge
Simon Alberti: Technische Universität Dresden
Tuomas P. J. Knowles: University of Cambridge

Nature Communications, 2022, vol. 13, issue 1, 1-10

Abstract: Abstract The assembly of biomolecules into condensates is a fundamental process underlying the organisation of the intracellular space and the regulation of many cellular functions. Mapping and characterising phase behaviour of biomolecules is essential to understand the mechanisms of condensate assembly, and to develop therapeutic strategies targeting biomolecular condensate systems. A central concept for characterising phase-separating systems is the phase diagram. Phase diagrams are typically built from numerous individual measurements sampling different parts of the parameter space. However, even when performed in microwell plate format, this process is slow, low throughput and requires significant sample consumption. To address this challenge, we present here a combinatorial droplet microfluidic platform, termed PhaseScan, for rapid and high-resolution acquisition of multidimensional biomolecular phase diagrams. Using this platform, we characterise the phase behaviour of a wide range of systems under a variety of conditions and demonstrate that this approach allows the quantitative characterisation of the effect of small molecules on biomolecular phase transitions.

Date: 2022
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DOI: 10.1038/s41467-022-35265-7

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