Phase transitions in soft matter: From colloidal suspensions to biomolecular condensate regulation

This thesis offers a comprehensive overview of recent advancements in the fields of soft matter computational physics and biophysics, emphasizing the intricate interplay between molecular interactions, phase transitions, and biological phenomena. Beginning with an exploration of polymorphic competition in hard spheres crystallization, we delve into the relative stability of different crystal phases, showing that subtle stability and interfacial free energy differences can dictate the nucleation behaviour of these colloidal systems. Continuing with different colloidal systems, we investigate the crystallization of oppositely charged colloids, where multiple polymorphs compete in the nucleation and crystal growth stages. By analyzing phase diagrams, nucleation and growth rates, we offer valuable insights into the complex behavior of colloidal systems and their significance across diverse industrial and biological applications. Continuing our study on phase transitions, we shift our focus to water, the most simple and ubiquitous biological fluid, and we discuss vapor-liquid equilibrium, bubble nucleation, and the characterization of liquid-vapor interfaces. By employing advanced computational techniques, we elucidate the underlying mechanisms driving these phase transitions, contributing to a deeper understanding of water's fundamental properties, such as the surface tension, or the interfacial arrangement of molecules. Another highly relevant phase transition, pertinent to biology, climate sciences, and material sciences, is the liquid-to-solid transition of water into ice, with applications such as cryopreservation and materials design. We examine homogeneous ice nucleation rates through Lattice Mold calculations, comparing different models and validating our findings against experimental data. This investigation not only enhances our understanding of ice formation but also provides valuable insights relevant to atmospheric processes and climate modeling. Moreover, we then make use of enhanced sampling techniques to measure the NaCl-water solution interfacial free energy, a measurement never attempted before due to its computational complications. Expanding our exploration of phase transitions with colloidal systems, we find common ground with the dynamic behavior of protein liquid-liquid phase separation by studying biophysical principles with different colloidal computational models for biomolecules. Our study of protein assemblies will therefore resemble previously investigated liquid-vapor transitions, highlighting shared principles between the self-organization of molecules in both colloidal and biological systems. In the context of multi-component protein condensates, we analyze the impact of protein valency and binding affinity on the molecular organization of condensates. We investigate how interfacial free energy acts as the driving force behind the organization of multilayered condensates and delve into the dynamics of species exchange within these intricate systems. Additionally, we explore how size conservation in biomolecular condensates can be sustained by the surfactant role of certain proteins, that modulate the surface tension of the condensates, resulting in protein assemblies with limited and defined sizes. Within intracellular biomolecular condensates, aside from proteins, we find other bio-molecules, being RNA one of the major ones that contribute to the stability, structure and function of condensates. Building on our investigation, we then explore RNA-protein condensates. Specifically, we examine the intricate effect of RNA on condensate stability, nucleation, and phase behavior by considering factors such as RNA length, concentration, and their impact on internal organization and interfacial properties. This research provides a mechanistic understanding of the regulatory pathways governing the formation, stability, and material properties of these dynamic biological assemblies. Finally, we investigate the potential role of intermolecular β-sheet formation in pathological protein aggregation, providing insights into potential strategies for regulating their emergence. The crucial development of an algorithm that recapitulates the formation of structured conformations within biomolecular condensates allows us to investigate challenging problems such as the pathological aggregation of proteins, namely FUS, TDP-43 hnRNPA1 and α1-antitrypsin. Finally, we aim to develop a computational framework to propose strategies to decelerate those structural transitions, which are commonly associated to the onset of neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and dementia. Through this interdisciplinary synthesis, this thesis highlights the importance of integrating principles from soft matter physics and biophysics to address complex biological questions.

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

• Sanchez Burgos, Ignacio

Advisors dc:contributor.advisor

• Rene Espinosa, Jorge
• Collepardo Guevara, rosana

• Nucleation
• Liquid-liquid phase separation
• Protein aggregation
• Interfaces
• Soft matter
• Computational biology

Licence

• https://www.repository.cam.ac.uk/bitstreams/7e82eb09-68c8-489d-afa9-365ca7ba1146/download
• https://creativecommons.org/licenses/by-nc-nd/4.0/

Language dc:language

eng

Author Identifier

0000-0002-1160-3945

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/379558