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Liquid-liquid phase separation (LLPS) of biomacromolecules is crucial in various inter and extracellular biological functions. This includes formation of condensates to control e.g. biochemical reactions and structural assembly. The same phenomenon is also found to be critically important in protein based high performance biological materials. Here, we use a well-characterized model triblock protein system to demonstrate the molecular level formation mechanism and structure of its condensate. Large-scale molecular modelling supported by analytical ultracentrifuge (AUC) characterization combined with our earlier high magnification precision cryo-SEM microscopy imaging lead to deducing that the condensate has a bicontinuous network structure. The bicontinuous network rises from the proteins having a combination of sites with stronger mutual attraction and multiple weakly attractive regions connected by flexible, multiconfigurational linker regions. These attractive sites and regions behave as stickers of varying adhesion strength. For the examined model triblock protein construct, the β-sheet rich end units are the stronger stickers while additional weaker stickers, contributing to the condensation affinity, rise from spring-like connections in the flexible middle region of the protein. The combination of stronger and weaker sticker-like connections and the flexible regions between the stickers result in a versatile, liquid-like, self-healing structure. This structure also explains the high flexibility, easy deformability and diffusion of the proteins decreasing only 10-100 times in the bicontinuous network formed in the condensate phase in comparison to dilute protein solution. The here demonstrated structure and condensation mechanism of a model triblock protein construct via a combination of the stronger binding regions and the weaker, flexible sacrificial-bond-like network, as well as its generalizability via polymer sticker models, provide means to understand not only intracellular organization, regulation, and cellular function but also identifies direct control factors for and enables engineering improved protein and polymer constructs to enhance control of advanced 3 fiber materials, smart liquid biointerfaces or self-healing matrices for pharmaceutics or bioengineering materials.

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The connection between the structure of solid solution and its spectroscopic and band parameters is discussed on the example of Zn,Cdl-,Se and Znl-,Mg,S systems with the structure phase transition: zinc blende (2B)-wurtzite (W). It is shown that if the E g ( x ) dependence is parabolic for the ZB and W pure structure ranges, it is linear in the phase transition range (for the Znl-,Mg,S system). Eg(z) is always higher for the anisotropic crystals (with stacking faults (SF) and W) than for the ZB ones depending on the more ionic character of their chemical bond. The influence of the disorder potential due t o composition 5 and SF concentration fluctuations on the exciton and band parameters of the solid solutions is considered.Die Verknupfung zwischen der Struktur der Mischkristalle und ihrer spektroskopischen und Bandparameter werden am Beispiel der Zn,Cdl -&e-und Znl -,Mg,S-Systeme mit dem strukturellen Phasenubergang Zinkblende (ZB)-Wurtzit (W) diskutiert. Es wird gezeigt, daB wenn die E&)-Abhangigkeit fur die reinen ZB-und W-Skrukturbereiche parabolisch ist, sie im Phaseniibergangsbereich (fur das Znl-,Mg,S-System) linear ist. Eg(z) ist immer groI3er fur die anisotropen Kristalle (mit Stapelfehler (SF) und W) als fur die ZB-Kristalle in AbhLngigkeit von dem hoheren ionischen Charakter ihrer chemischen Bindung. Der EinfluB des Fehlordnungspotentials, das aus den Zusammensetzungs (z)-und SF-Konzentrationsfluktuationen herruhrt, anf die Exzitonenund Bandparameter der Mischkristalle wird diskutiert.

The limited diversity in targets of available antibiotic therapies has put tremendous pressure on the treatment of bacterial pathogens, where numerous resistance mechanisms that counteract their function are becoming increasingly prevalent. Here, we utilize an unconventional anti-virulence screen of host-guest interacting macrocycles, and identify a water-soluble synthetic macrocycle, Pillar[5]arene, that is non-bactericidal/bacteriostatic and has a mechanism of action that involves binding to both homoserine lactones and lipopolysaccharides, key virulence factors in Gram-negative pathogens. Pillar[5]arene is active against Top Priority carbapenem- and third/fourth-generation cephalosporin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, suppressing toxins and biofilms and increasing the penetration and efficacy of standard-of-care antibiotics in combined administrations. The binding of homoserine lactones and lipopolysaccharides also sequesters their direct effects as toxins on eukaryotic membranes, neutralizing key tools that promote bacterial colonization and impede immune defenses, both in vitro and in vivo. Pillar[5]arene evades both existing antibiotic resistance mechanisms, as well as the build-up of rapid tolerance/resistance. The versatility of macrocyclic host-guest chemistry provides ample strategies for tailored targeting of virulence in a wide range of Gram-negative infectious diseases.