Protein solutions approaching phase separation and dynamical arrest
Final Report Abstract
If protein molecules are very close to each other, they will likely experience a mutual attraction. Thus, many proteins can clump together in so-called condensed states. For example, droplets containing many proteins can act like syrupy liquids inside a biological cell, forming specialized cellular parts without being separated by a membrane. These droplets can form via a process called liquid-liquid phase separation (LLPS). This means that a protein solution changes from a homogeneous state to another state composed of two coexisting liquids, one enriched and one depleted in proteins. This condensation process is not only relevant in cell biology, but also in many other fields, including medicine, pharmaceutics, materials science and physics. However, proteins are very complex and large molecules and, consequently, they can interact with each other in a complicated manner, but these highly complex interactions govern the condensation process. From a physics perspective, it would be intriguing to provide a rationale for the interactions of proteins under conditions that can lead to LLPS. Indeed, for much simpler model systems, it has been suggested that, close to LLPS, many properties of the solutions are not sensitive to the molecular details, but can be effectively described by only few parameters. However, whether this idea also applies to protein solutions with their complex interactions has not been tested systematically. In this project, we have performed comprehensive light and X-ray scattering as well as optical microscopy experiments for solutions with different protein concentrations, temperatures and additive contents. We were thus able to characterize under which conditions LLPS occurs and, in particular, how the spatial organization of the proteins as well as their collective motion depend on the solution conditions. Our quantitative experimental data demonstrate that close to LLPS only few global parameters determine the structure and collective dynamics of protein solutions as well as which state the solution attains. Our results thus confirm that the so-called extended law of corresponding states applies to protein solutions. Moreover, we could thus justify why models, inspired by much simpler systems, can adequately describe such complex systems as protein solutions. We believe that our work contributes to a deeper understanding of protein condensation in general and might be relevant for the various fields in which LLPS is encountered.
Publications
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Interactions in protein solutions close to liquid–liquid phase separation: ethanol reduces attractions via changes of the dielectric solution properties. Physical Chemistry Chemical Physics, 23(39), 22384-22394.
Hansen, Jan; Uthayakumar, Rajeevann; Pedersen, Jan Skov; Egelhaaf, Stefan U. & Platten, Florian
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The crystallization enthalpy and entropy of protein solutions: microcalorimetry, van't Hoff determination and linearized Poisson–Boltzmann model of tetragonal lysozyme crystals. Physical Chemistry Chemical Physics, 23(4), 2686-2696.
Hentschel, Lorena; Hansen, Jan; Egelhaaf, Stefan U. & Platten, Florian
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Universal effective interactions of globular proteins close to liquid–liquid phase separation: Corresponding-states behavior reflected in the structure factor. The Journal of Chemical Physics, 156(24).
Hansen, Jan; Pedersen, Jannik N.; Pedersen, Jan Skov; Egelhaaf, Stefan U. & Platten, Florian
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Phase separation and dynamical arrest of protein solutions dominated by short-range attractions. The Journal of Chemical Physics, 158(2).
Hansen, Jan; Moll, Carolyn J.; López, Flores Leticia; Castañeda-Priego, Ramón; Medina-Noyola, Magdaleno; Egelhaaf, Stefan U. & Platten, Florian
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Protein solutions close to liquid–liquid phase separation exhibit a universal osmotic equation of state and dynamical behavior. Physical Chemistry Chemical Physics, 25(4), 3031-3041.
Hansen, Jan; Egelhaaf, Stefan U. & Platten, Florian
