Role of Solvent Compatibility in the Phase Behavior of Binary Solutions of Weakly Associating Multivalent Polymers.

Condensate formation of biopolymer solutions, prominently those of various intrinsically disordered proteins (IDPs), is often driven by "sticky" interactions between associating residues, multivalently present along the polymer backbone. Using a ternary mean-field "stickers-and-spacers" model, we demonstrate that if sticker association is of the order of a few times the thermal energy, a delicate balance between specific binding and nonspecific polymer-solvent interactions gives rise to a particularly rich ternary phase behavior under physiological circumstances. For a generic system represented by a solution comprising multiassociative scaffold and client polymers, the difference in solvent compatibility between the polymers modulates the nature of isothermal liquid-liquid phase separation (LLPS) between associative and segregative. The calculations reveal regimes of dualistic phase behavior, where both types of LLPS occur within the same phase diagram, either associated with the presence of multiple miscibility gaps or a flip in the slope of the tie-lines belonging to a single coexistence region.

Contract award criteria in public procurement procedures - The possibility of improving the situation of society from the perspective of the European Union and Poland.

Background: Public tenders are vital for a country's GDP and citizens' quality of life, enabling public administration to achieve various goals. Developing and developed countries allocate over 10% of their GDP to public procurement. This highlights the significant societal support public tenders can provide, making it important to consider how they can further benefit society. Policy and implications: Public procurement can achieve policy objectives and benefit society by selecting tenders based on criteria beyond price, such as economic advantage and social benefits. This approach, endorsed by EU directives since 2014, encourages innovation and socially responsible practices. Contracting authorities in the EU can use social, environmental, and qualitative criteria to determine the most advantageous offers.Poland's Public Procurement Law (PPL) allows contract award criteria based on quality and price, including social aspects. Contracting authorities can specify criteria like employing marginalized groups, though these criteria often face scrutiny and legal challenges. Non-price criteria aim to enhance competition and achieve social, environmental, and economic goals. Recommendations: EU and Polish laws permit and encourage using social aspects as contract award criteria in public procurement. However, contracting authorities must analyze priorities, risk balancing, time constraints, and departmental coordination to effectively implement these criteria. This approach can improve the social situation and support specific groups. Conclusions: Public procurement significantly influences a country's economy and quality of life, with EU and Polish laws allowing social criteria in contract awards. Directive 2014/24/EU supports tenders based on economic and social benefits. Poland's PPL aligns with this, emphasizing marginalized group employment. Effective implementation fosters job creation, social integration, and improved living standards.

Fibril formation and ordering of disordered FUS LC driven by hydrophobic interactions.

Biomolecular condensates, protein-rich and dynamic membrane-less organelles, play critical roles in a range of subcellular processes, including membrane trafficking and transcriptional regulation. However, aberrant phase transitions of intrinsically disordered proteins in biomolecular condensates can lead to the formation of irreversible fibrils and aggregates that are linked to neurodegenerative diseases. Despite the implications, the interactions underlying such transitions remain obscure. Here we investigate the role of hydrophobic interactions by studying the low-complexity domain of the disordered 'fused in sarcoma' (FUS) protein at the air/water interface. Using surface-specific microscopic and spectroscopic techniques, we find that a hydrophobic interface drives fibril formation and molecular ordering of FUS, resulting in solid-like film formation. This phase transition occurs at 600-fold lower FUS concentration than required for the canonical FUS low-complexity liquid droplet formation in bulk. These observations highlight the importance of hydrophobic effects for protein phase separation and suggest that interfacial properties drive distinct protein phase-separated structures.

Reversible Kinetic Trapping of FUS Biomolecular Condensates.

Formation of membrane-less organelles by self-assembly of disordered proteins can be triggered by external stimuli such as pH, salt, or temperature. These organelles, called biomolecular condensates, have traditionally been classified as liquids, gels, or solids with limited subclasses. Here, the authors show that a thermal trigger can lead to formation of at least two distinct liquid condensed phases of the fused in sarcoma low complexity (FUS LC) domain. Forming FUS LC condensates directly at low temperature leads to formation of metastable, kinetically trapped condensates that show arrested coalescence, escape from which to untrapped condensates can be achieved via thermal annealing. Using experimental and computational approaches, the authors find that molecular structure of interfacial FUS LC in kinetically trapped condensates is distinct (more ß-sheet like) compared to untrapped FUS LC condensates. Moreover, molecular motion within kinetically trapped condensates is substantially slower compared to that in untrapped condensates thereby demonstrating two unique liquid FUS condensates. Controlling condensate thermodynamic state, stability, and structure with a simple thermal switch may contribute to pathological protein aggregate stability and provides a facile method to trigger condensate mixing for biotechnology applications.