Biomolecular condensate phase diagrams with a combinatorial microdroplet platform

被引：44

作者：

Arter, William E. ^{[1
]}

Qi, Runzhang ^{[1
]}

Erkamp, Nadia A. ^{[1
]}

Krainer, Georg ^{[1
]}

Didi, Kieran ^{[1
]}

Welsh, Timothy J. ^{[1
]}

Acker, Julia ^{[2
]}

Nixon-Abell, Jonathan ^{[3
]}

Qamar, Seema ^{[3
]}

Guillen-Boixet, Jordina ^{[4
]}

Franzmann, Titus M. ^{[4
]}

Kuster, David ^{[5
]}

Hyman, Anthony A. ^{[5
]}

Borodavka, Alexander ^{[2
]}

George-Hyslop, Peter St ^{[3
,6
,7
,8
]}

Alberti, Simon ^{[4
]}

Knowles, Tuomas P. J. ^{[1
,9
]}

机构：

[1] Univ Cambridge, Yusuf Hamied Dept Chem, Ctr Misfolding Dis, Lensfield Rd, Cambridge CB2 1EW, England

[2] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England

[3] Univ Cambridge, Cambridge Inst Med Res, Dept Clin Neurosci, Cambridge CB2 0XY, England

[4] Tech Univ Dresden, Biotechnol Ctr BIOTEC, Ctr Mol & Cellular Bioengn CMCB, Tatzberg 47-49, D-01307 Dresden, Germany

[5] Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany

[6] Univ Toronto, Dept Med, Div Neurol, Toronto, ON M5S 3H2, Canada

[7] Univ Hlth Network, Toronto, ON M5S 3H2, Canada

[8] Columbia Univ, Dept Neurol, 630West 168th St, New York, NY 10032 USA

[9] Univ Cambridge, Dept Phys, Cavendish Lab, J J Thomson Ave, Cambridge CB3 0HE, England

来源：

NATURE COMMUNICATIONS | 2022年 / 13卷 / 01期

基金：

英国惠康基金; 英国工程与自然科学研究理事会; 加拿大健康研究院; 欧洲研究理事会;

关键词：

LIQUID; SEPARATION; TRANSITION;

D O I：

10.1038/s41467-022-35265-7

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 64 条

[1] Ultrahigh-throughput screening in drop-based microfluidics for directed evolution [J].