Self-crowding induced phase separation in protein dispersions

Abstract

The coupling between protein conformation, molecular volume, and solution phase behaviour is studied theoretically for a two-state, coarse-grained protein model in which protein molecules can reversibly switch between a native and a non-native excited state. In the model, native and non-native conformers are represented by perfect spheres with different hard-core diameters. We presume the larger, non-native species to attract each other through some unspecified potential. We find that at low concentrations the native state is stabilised energetically and that at high concentrations the native state is again stabilised but this time by self-crowding, i.e., a lack of free volume. These two regimes are separated by two first-order transitions from a region where the non-native conformational state is prevalent, stabilised by attractive interactions between the proteins. The calculated phase diagram is very sensitive to even quite small differences in particle volumes and has unusual features, including the loss of a critical point if the size difference is sufficiently large. C 2015 AIP Publishing LLC. [http://dx

Osmolyte accumulation regulates the SUMOylation and inclusion dynamics of the prionogenic Cyc8-Tup1 transcription corepressor

“…As such, organisms have evolved fast biophysical mechanisms to expedite slower biochemical responses during adaptation, as seen with the yeast proteins Pab1 and Sup35 that condense into focal structures during stress conditions [15, 29]. Hyperosmotic stress causes significant water efflux from cells, decreasing the total cellular volume and increasing macromolecular crowding [30], which has been implicated as an important factor in the condensation of protein-RNA complexes into phase separated droplets in vitro [31]. Moreover, it is well documented that hyperosmotic stress drives the formation of various cytoplasmic membraneless organelles, including stress granules in yeast and P granules in Caenorhabditis elegans [32, 33].…”

Active interaction switching controls the dynamic heterogeneity of soft colloidal dispersions

“…The environment-dependent size of responsive materials can change by a factor of two or three typically 6 . Examples of this are globular proteins, in which their conformation and phase behavior can be tuned by changes in the local environment and protein-protein attractive interaction 7,8 . These colloidal systems and their responsiveness can be used for tailormade functionality such as core-shell nano-reactors for selective catalysis 3,4 or controlled drug release 1,2 , but also lay the foundation for adaptive and intelligent systems 9 .…”

“…Such a system constitutes a good model for bistable bacteria that use switching to tune structural and dynamical heterogeneities for their function 37,38 , as well as for soft active or vesicles fluctuating between two states [39][40][41][42] . It could also be applied to study the structure and phase behavior of conformationally fluctuating biopolymers [43][44][45] , in particular two-state proteins switching between native and non-native states 7,8 . In future it may be extendable to even study soft micromachines with a programmable morphology 46 .…”