German Edition: DOI: 10.1002/ange.201805021 Nanoreactors International Edition: DOI: 10.1002/anie.201805021 Enzyme-Compatible Dynamic Nanoreactors from Electrostatically Bridged Like-Charged Surfactants and Polyelectrolytes Martin J. Thiele, Mehdi D. Davari, Isabell Hofmann, Melanie Kçnig, Carlos G. Lopez, Ljubica Vojcic, Walter Richtering, Ulrich Schwaneberg, and Larisa A. Tsarkova* Abstract: Reported is an unanticipated mechanism of attrac- tive electrostatic interactions of fully neutralized polyacrylic acid (PAA) with like-charged surfactants. Amphiphilic poly- mer-surfactant complexes with high interfacial activity and a solubilization capacity exceeding that of conventional micelles are formed by bridging with Ca 2+ ions. Incorporation of a protease into such dynamic nanoreactors results in a synergistically enhanced cleaning performance because of the improved solubilization of poorly water-soluble immobi- lized proteins. Competitive interfacial and intermolecular interactions on different time- and length-scales have been resolved using colorimetric analysis, dynamic tensiometry, light scattering, and molecular dynamic simulations. The discovered bridging association mechanism suggests reengin- eering of surfactant/polymer/enzyme formulations of modern detergents and opens new opportunities in advancing labile delivery systems. Association colloids such as micelles, vesicles, or aggregates of surfactants with either synthetic polymers or biopoly- mers, [1] play an important role in modern technologies, including pharmaceuticals and cosmetics, food, laundry, and home care. [2] A variety of self-assembled phases can be formed by multiple, competitive physical or chemical supra- molecular interactions, including electrostatic and van der Waals forces, hydrogen bonding, hydrophobic and excluded volume effects, as well as intermolecular crosslinking. [1c, 2a, 3] Such diversity calls for multidisciplinary research strategies, both experimental [1c,d, 4] and computational, [5] to understand the mechanisms of self-assembly and functions of polymer- surfactant supramolecular complexes. Traditional experimen- tal approaches are based on the evaluation of changes in the macroscopic properties of solutions such as viscosity, surface tension, etc., as a result of polymer–surfactant interactions. In the case of biomacromolecules, for example, enzymes, common methodologies to study polymer–surfactant inter- actions are based on the analysis of the effect of the surfactant on the catalytic performance of the enzyme. [4b, 6] Several studies on systems containing similarly charged surfactants (either anionic or cationic) and polyelectrolytes reported an association of surfactants with nonpolar segments of hydrophobically modified polyelectrolytes resulting from pure hydrophobic interactions. [7] All these studies, however, pointed out the absence of ionic binding as a result of unfavorable electrostatic repulsion in these systems. [8] In accordance with the increasing demands for efficient detergent formulations, we report a macroscopic, statistically reproducible effect of improved solubilization of hydrophobic immobilized proteins by a complex system containing a poly- acrylic acid (PAA), sodium lauryl ether sulfate (SLES) ethoxylated surfactant, and a protease enzyme (subtilisin protease PDB ID : 1ST3 [9] ) in the presence of Ca 2+ /Mg 2+ ions. Subtilisin proteases are nonspecific proteases commonly used in detergents to remove protein stains in the presence of Ca 2+ / Mg 2+ ions. [10] The employed solubility tests address, on different time scales, a number of interfacial phenomena such as wetting of the cotton surface and desorption of the hydrophobic dye, as well as the formation of a new liquid- liquid interface for effective solubilization of the hydrophobic protein. Molecular interactions guiding the self-assembly of the SLES/PAA/Ca 2+ components have been assessed with molecular dynamics (MD) simulations and light-scattering experiments. Dynamic surface tension measurements deliv- ered decisive insights with regard to the functional properties of the electrostatically bridged complexes between like- charged polymers and surfactants. The experimental system sketched in Figure 1 A mimics a miniaturized washing procedure which involves concurrent interfacial processes at solid-liquid and liquid-liquid inter- faces. Absorbance spectra of model systems containing either individual components or a combination thereof are corre- lated with the efficiency of each studied system to extract a dye from the surface and to solubilize it in solution. The two employed aqueous environments, each with a total ionic strength of 11 mmol, are denoted as 08dGH, soft water, and 158dGH, hard water (see Table S1 in the Supporting Infor- [*] M. J. Thiele, [++] Dr. M. D. Davari, [++] I. Hofmann, M. Kçnig, Dr. L. Vojcic, Prof.Dr. U. Schwaneberg Institute of Biotechnology, RWTH Aachen University Worringerweg 3, 52056 Aachen (Germany) Dr. C. G. Lopez, Prof. Dr. W. Richtering Institute of Physical Chemistry II, RWTH Aachen University 52056 Aachen (Germany) Prof. Dr. U. Schwaneberg 3DWI-Leibniz Institute for Interactive Materials Forckenbeckstraße 50, 52056 Aachen (Germany) Dr. L. A. Tsarkova Faculty of Chemistry, Chair of Colloid Chemistry Moscow State University 1–3 Leninskiye Gory, 119991 Moscow (Russia) E-mail: tsarkova@colloid.chem.msu.ru Dr. L. A. Tsarkova Deutsches Textilforschungszentrum Nord-West GmbH (DTNW) 47798 Krefeld (Germany) [ ++ ] joint first author contribution Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201805021. A ngewandte Chemi e Communications 1 Angew. Chem. Int. Ed. 2018, 57,1–7  2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim These are not the final page numbers! Ü Ü