Biology subjects

Scrutton, R. M.

Publications and source records attributed to Scrutton, R. M..

3 recordsLinked to original sources

bioRxiv2026

Many-body Interaction Competition Drives Reentrant Phase Transitions

Reentrant phase transitions, in which multicomponent systems phase separate at intermediate concentrations but dissolve at experimentally accessible higher concentrations, are ubiquitous in mixtures such as biomolecular condensates. We show that introducing reversible dimerization into a multicomponent Flory-Huggins model and integrating out the dimer state generate an effective three-body repulsion that reshapes phase diagram geometry. This emergent higher-order interaction arises naturally from an interaction competition and mass-action equilibrium, providing a microscopic explanation to the previously phenomenological three-body interaction. We derive a closed-form phase boundary equation capturing phase separation and reentrant dissolution in this minimal model, and predict explicit interdependence between competition strength, emergent many-body interactions, and dissociation constants. We recover and extend the reentrant phase boundary scaling relations through interaction renormalization, with regime of validity. We apply our model to G3BP1-RNA-suramin and explain the underlying mechanisms from the physical parameters inferred from reentrant phase boundaries.

biophysics↗

bioRxiv2026

Lipoengineering of Biomolecular Condensates Controls Material Properties and Multiphase Hierarchy to Guide Organoid Morphogenesis

Cells use post-translational modifications (PTMs) to reconfigure biomolecular condensates across length scales, space, and time.1,2 While charged PTMs are well-known electrostatic switches,3,4 how ubiquitous neutral PTMs shape condensate plasticity and hierarchy remains unclear. Here, we establish a set of design principles for using site-specific lipidation, a class of neutral hydrophobic PTMs, to rationally control properties and interactions of engineered biomolecular condensates. Through systematic analysis of over 80 lipidated synthetic intrinsically disordered proteins (IDPs), we uncovered two distinct axes of control. First, the interplay between the lipid and the local three-residue sequence of its attachment site acts as a programmable switch for cohesion--the homotypic interactions that define the material state of the condensed phase-- directing assemblies toward dynamic liquids, arrested gels, or ordered fibrillar solids. Second, the lipid, together with the global properties of the IDP scaffold, tunes adhesion--the heterotypic interactions that govern condensate miscibility and hierarchical organization. We harnessed these principles to rationally engineer complex, multi-phase architectures and create hybrid hydrogels with programmed microstructure and material properties that guide the morphogenesis of functional intestinal organoids. These findings establish a new framework for lipoengineering advanced biomaterials and provide a blueprint for dissecting structure-property relationships across diverse classes of PTMs.

bioengineering↗

bioRxiv2024

Biomolecular condensates sustain pH gradients at equilibrium driven by charge neutralisation

Electrochemical gradients are essential to the functioning of cells and form across membranes using active transporters. Here, we show in contrast that condensed biomolecular systems sustain significant pH gradients without any external energy input. By studying individual condensates on the micron scale using a microdroplet platform, we reveal dense phase pH shifts towards conditions of minimal electrostatic repulsion. We demonstrate that by doing so protein condensates can drive substantial alkaline and acidic gradients which are compositionally tuneable and can extend to complex architectures sustaining multiple unique pH conditions simultaneously. Through in silico characterisation of human proteomic condensate networks, we further highlight potential wide ranging electrochemical properties emerging from condensation in nature, while correlating intracellular condensate pH gradients with complex biomolecular composition. Together, the emergent nature of condensation shapes distinct pH microenvironments, thereby creating a unique regulatory mechanism to modulate biochemical activity in living systems.

biophysics↗