Understanding and designing complex architectures of biomolecular condensates

Biomolecular condensates emerge when a homogeneous liquid phase separates into the condensate and a dilute phase. Condensates in cells function as membrane-less organelles and perform a variety of (temporary) functions. They may also be involved with pathological processes, like the progression of neurodegenerative diseases. Additionally, they are of interest for various bioengineering applications such as drug delivery and synthetic biology research. The mesoscale architecture of condensates, how different phases are organized compared to each other, is intimately connected to their function. However, very little tools are available to control the structure. In my thesis, I establish methods for understanding and controlling different mesoscale architectures of condensates. Firstly, I have worked on the development of microfluidic methods to measure phase diagrams. These allowed us to measure protein solubility and tie lines, as well as understand when and how condensates form. Then, I studied the nucleation of droplets in liquid-like condensates, including the nucleation of the dilute phase and dense phase droplets. Lastly, I've applied the developed techniques to work on a biological problem: the use of phase separating antimicrobial peptides. Overall, my findings and developments provide understanding and control over condensate architecture in a range of condensate systems with direct implications of therapeutic interventions.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Erkamp, Nadia

Advisor dc:contributor.advisor

• Knowles, Tuomas

• biomolecular condensates
• Dynamics
• Microfluidics
• Phase diagram

Licence

• https://www.repository.cam.ac.uk/bitstreams/90978f09-fed2-477b-82af-a84a1af2f12e/download
• https://creativecommons.org/licenses/by/4.0/

Language dc:language

eng

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.111884

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/373498