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Design of biologically active binary protein 2D materials.

ABSTRACT: Ordered two-dimensional arrays such as S-layers^1,2 and designed analogues^3-5 have intrigued bioengineers^6,7, but with the exception of a single lattice formed with flexible linkers⁸, they are constituted from just one protein component. Materials composed of two components have considerable potential advantages for modulating assembly dynamics and incorporating more complex functionality^9-12. Here we describe a computational method to generate co-assembling binary layers by designing rigid interfaces between pairs of dihedral protein building blocks, and use it to design a p6m lattice. The designed array components are soluble at millimolar concentrations, but when combined at nanomolar concentrations, they rapidly assemble into nearly crystalline micrometre-scale arrays nearly identical to the computational design model in vitro and in cells without the need for a two-dimensional support. Because the material is designed from the ground up, the components can be readily functionalized and their symmetry reconfigured, enabling formation of ligand arrays with distinguishable surfaces, which we demonstrate can drive extensive receptor clustering, downstream protein recruitment and signalling. Using atomic force microscopy on supported bilayers and quantitative microscopy on living cells, we show that arrays assembled on membranes have component stoichiometry and structure similar to arrays formed in vitro, and that our material can therefore impose order onto fundamentally disordered substrates such as cell membranes. In contrast to previously characterized cell surface receptor binding assemblies such as antibodies and nanocages, which are rapidly endocytosed, we find that large arrays assembled at the cell surface suppress endocytosis in a tunable manner, with potential therapeutic relevance for extending receptor engagement and immune evasion. Our work provides a foundation for a synthetic cell biology in which multi-protein macroscale materials are designed to modulate cell responses and reshape synthetic and living systems.

SUBMITTER: Ben-Sasson AJ

PROVIDER: S-EPMC7855610 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Thiazol-based molecules have practically infinite biological implementation. Today, there are many medical applications for compounds containing the thiazole moiety owing to their presence in most clinically applied anticancer drugs, such as dasatinib, dabrafenib, ixabepilone, patellamide A and epothilone. In this study, the polycondensation, of a new group of thiazole-containing polyamides with the formulas PA1-4 was carried out by the interaction of 2-aminothiazole diphenyl sulfide and variable diacid chlorides in dimethyl formamide in the presence of potassium carbonate anhydrous as a catalyst. Fourier transform-infrared spectroscopy (FTIR) was initially used to figure out the PA1-4 structures, which were further characterized using solubility, gel permeation chromatography (GPC), X-ray diffraction analyses (XRD) and scanning electron microscopy (SEM). The solubility results revealed that the presence of heteroaromatic thiazole ring units and sulfur content in the polyamides main chain, made the solubility easier as it increases the chain packing distance. From the values of average molecular weight, it was clear that all synthesized polyamides have almost the same chain length which ranged from 37,561.80 to 39,827.66. Moreover, the thermogravimetric analysis (TGA) confirm that PA1-4 were thermally stable even at high temperatures especially the polyamides which were synthesized from aromatic diacid chlorides. Furthermore, the newly synthesized polyamides were investigated for their antimicrobial properties against different species of Gram-positive and Gram-negative bacteria and also against different fungi. The results revealed that compound PA2 showed the highest antibacterial activity. Also, their inhibitory activity against breast carcinoma cells (MCF-7 cell line) and colon carcinoma cells (HCT cell line) was evaluated. It was clear that there was an enhancement in the anticancer activity for the synthesized polyamides owing to the presence of the thiazole moiety as well as sulfur linkage. According to the results of the 50% inhibitory concentration (IC50), the synthesized polymers were found to be more active against the MCF-7 cell line than the HCT cell line.

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Design of biologically active binary protein 2D materials.

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