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Biomolecular function and failure across length scales https://doi.org/10.17863/CAM.116851 Ausserwoeger, Hannes Knowles, Tuomas PJ Nature has evolved proteins to form the fundamental machinery of life through controlled assembly. Such protein assembly can span five orders of magnitude in length scale, from subnanometer intramolecular arrangements to the formation of micron- sized compartments. However, our understanding of protein assembly has largely been confined to the structural organisation and pairwise interactions of individual proteins at the nanoscale. In this thesis, I explore protein assembly processes that transcend the molecular scale, emphasising their significance in functional biological processes and therapeutic intervention strategies. Firstly, this thesis establishes a set of methodological advancements capable of addressing current limitations in the study of protein condensation and aggregation, to tackle fundamental biological questions and enable disease biomarker detection. These advancements enable the discovery of previously unexplored emergent protein functions arising from condensation, such as the formation of electrochemical gradients and antimicrobial activity. Furthermore, this thesis advances our grasp of protein assembly specificity by controlling surface chemistry to improve development pipelines of protein therapeutics. Overall, this work expands our understanding of biomolecular function and malfunction, providing tools to decode protein behavior across length scales and guiding future therapeutic intervention strategies. University of Cambridge 2024-09-28 Thesis Doctoral Doctor of Philosophy (PhD) eng Global Research Technologies, Novo Nordisk A/S European Research Council under the European Union’s Horizon 2020 research and innovation program through the ERC grant DiProPhys (agreement ID 101001615) https://www.repository.cam.ac.uk/handle/1810/381784 embargo 2026-03-21 https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/a03aee32-1844-42c0-ac9e-c5f45bb903c2/download d3034cb0588d243a15539735ccdaaf0a https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/4ce89867-0f82-495a-9e62-44e7f23039c4/download 87eda9de84448d1f82354d60eee3eb5f http://purl.org/NET/rdflicense/allrightsreserved Biophysics Condensation Drug development Misfolding disease Protein phase transitions