Engineered Living Materials based on Adhesin-mediated Trapping of Programmable Cells
Shuaiqi GuoiD, Emilien Dubuc, Yahav Rave, Mick Verhagen, Simone A. E. Twisk, Tim van der HekiD, Guido J.M. OerlemansiD, Maxime C. M. van den OetelaariD, Laura S. van HazendonkiD, Mariska BrülsiD, Bruno V. Eijkens, Pim L. Joostens, Sander R. Keij, Weizhou Xing, Martijn Nijs, Jitske Stalpers, Manoj Kumar SharmaiD, Marieke GerthiD, Roy J. E. A. BooneniD, Kees Verduin, Maarten MerkxiD, Ilja Karina VoetsiD, Tom F. A. de GreefiD
Abstract
Engineered living materials have the potential for wide-ranging applications such as biosensing and treatment of diseases. Programmable cells provide the functional basis for living materials, however, their release into the environment raises numerous biosafety concerns. Current designs that limit the release of genetically engineered cells typically involve the fabrication of multi-layer hybrid materials with sub-micron porous matrices. Nevertheless the stringent physical barriers limit the diffusion of macromolecules and therefore the repertoire of molecules available for actuation in response to communication signals between cells and their environment. Here, we engineer a first-of-its-kind living material entitled Platform for Adhesin-mediated Trapping of Cells in Hydrogels (PATCH). This technology is based on engineered E. coli that displays an adhesion protein derived from an Antarctic bacterium with high affinity for glucose. The adhesin stably anchors E. coli in dextran-based hydrogels with large pore diameters (10-100 m) and reduces the leakage of bacteria into the environment by up to 100-fold. As an application of PATCH, we engineered E. coli to secrete lysostaphin via the Type 1 Secretion System and demonstrated that living materials containing this E. coli inhibit the growth of S. aureus, including the strain resistant to methicillin (MRSA). Our tunable platform allows stable integration of programmable cells in dextran-based hydrogels without compromising free diffusion of macromolecules and could have potential applications in biotechnology and biomedicine.
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