Bottom-up assembly of target-specific cytotoxic synthetic cells

Jochen Estebano Hernandez Bücher; Oskar Staufer; Lukas Ostertag; Ulrike Mersdorf; Ilia  Platzman; Joachim Pius  Spatz

doi:10.1016/j.biomaterials.2022.121522

Bottom-up assembly of target-specific cytotoxic synthetic cells

Jochen Estebano Hernandez Bücher
, Oskar Staufer^*
, Lukas Ostertag
, Ulrike Mersdorf
, Ilia Platzman^*
, Joachim Pius Spatz^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

30 Citations (Scopus)

Abstract

Immune vigilance ensures body integrity by eliminating malignant cells through the complex but coordinated cooperation of highly diversified lymphocytes populations. The sheer complexity of the immune system has slowed development of immunotherapies based on top-down genetic engineering of lymphocytes. In contrast, bottom-up assembly of synthetic cell compartments has contributed novel engineering strategies to reverse engineer and understand cellular phenomena as molecularly defined systems. Towards reducing the complexity of immunological systems, herein, a bottom-up approach for controlled assembly of fully-synthetic immune-inspired cells from predefined molecular components based on giant unilamellar vesicles is described. For construction of target-specific cytotoxic immune cells, the Fas-ligand-based apoptosis-inducing immune cell module is combined with an antibody-mediated cellular cytotoxicity-inspired system. The designed immune cells identify leukemia cells by specific surface antigens. Subsequently, they form stable attachments sites and eliminate their targets by induction of apoptosis. A structural and functional characterization of the synthetic immune cells by means of microfluidics, live cell, confocal and electron microscopy, dynamic light scattering as well as flow cytometry is presented. This study demonstrates the bioinspired construction of effector immune cells from defined molecular building blocks, enabling learning-by-building approaches in synthetic immunology.

Original language	English
Article number	121522
Journal	Biomaterials
Volume	285
DOIs	https://doi.org/10.1016/j.biomaterials.2022.121522
Publication status	Published - 13 Apr 2022

Bibliographical note

Funding Information:
The authors acknowledge funding from the Federal Ministry of Education and Research of Germany, Grant Agreement no. 13XP5073A , PolyAntiBak and the MaxSynBio Consortium, the latter is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society . They also acknowledge the support from the Volkswagen Stiftung (priority call ‘Life?‘), the German Science Foundation SFB 1129 and the Deutsche Forschungsgemeinschaft ( DFG , German Research Foundation) under Germany's Excellence Strategy via the Excellence Cluster 3D Matter Made to Order ( EXC-2082/1–390761711 ). The authors are grateful to Julia Ricken for production and purification of recombinant GFP. J.P.S. acknowledge funding from the Gottfried Wilhelm Leibniz Award. J.E.H.B is grateful to Prof. Johannes Herrmann (Technical University of Kaiserslautern , Germany) for continuous support and critical discussion of the data. J.E.H.B. and O.S. acknowledge support from the Heidelberg Biosciences International Graduate School. O.S. acknowledges support from the Max Planck School Matter to Life and the Joachim Herz Foundation (add-on fellowship). O.S. is the Meurer Visiting Professor at the Max Planck Center for Minimal Biology, Bristol. The Max Planck Society is appreciated for its general support.

Publisher Copyright:
© 2022 The Authors

Research Groups and Themes

Max Planck Bristol
Bristol BioDesign Institute

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title = "Bottom-up assembly of target-specific cytotoxic synthetic cells",

abstract = "Immune vigilance ensures body integrity by eliminating malignant cells through the complex but coordinated cooperation of highly diversified lymphocytes populations. The sheer complexity of the immune system has slowed development of immunotherapies based on top-down genetic engineering of lymphocytes. In contrast, bottom-up assembly of synthetic cell compartments has contributed novel engineering strategies to reverse engineer and understand cellular phenomena as molecularly defined systems. Towards reducing the complexity of immunological systems, herein, a bottom-up approach for controlled assembly of fully-synthetic immune-inspired cells from predefined molecular components based on giant unilamellar vesicles is described. For construction of target-specific cytotoxic immune cells, the Fas-ligand-based apoptosis-inducing immune cell module is combined with an antibody-mediated cellular cytotoxicity-inspired system. The designed immune cells identify leukemia cells by specific surface antigens. Subsequently, they form stable attachments sites and eliminate their targets by induction of apoptosis. A structural and functional characterization of the synthetic immune cells by means of microfluidics, live cell, confocal and electron microscopy, dynamic light scattering as well as flow cytometry is presented. This study demonstrates the bioinspired construction of effector immune cells from defined molecular building blocks, enabling learning-by-building approaches in synthetic immunology.",

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note = "Funding Information: The authors acknowledge funding from the Federal Ministry of Education and Research of Germany, Grant Agreement no. 13XP5073A , PolyAntiBak and the MaxSynBio Consortium, the latter is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society . They also acknowledge the support from the Volkswagen Stiftung (priority call {\textquoteleft}Life?{\textquoteleft}), the German Science Foundation SFB 1129 and the Deutsche Forschungsgemeinschaft ( DFG , German Research Foundation) under Germany's Excellence Strategy via the Excellence Cluster 3D Matter Made to Order ( EXC-2082/1–390761711 ). The authors are grateful to Julia Ricken for production and purification of recombinant GFP. J.P.S. acknowledge funding from the Gottfried Wilhelm Leibniz Award. J.E.H.B is grateful to Prof. Johannes Herrmann (Technical University of Kaiserslautern , Germany) for continuous support and critical discussion of the data. J.E.H.B. and O.S. acknowledge support from the Heidelberg Biosciences International Graduate School. O.S. acknowledges support from the Max Planck School Matter to Life and the Joachim Herz Foundation (add-on fellowship). O.S. is the Meurer Visiting Professor at the Max Planck Center for Minimal Biology, Bristol. The Max Planck Society is appreciated for its general support. Publisher Copyright: {\textcopyright} 2022 The Authors",

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doi = "10.1016/j.biomaterials.2022.121522",

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AU - Hernandez Bücher, Jochen Estebano

AU - Staufer, Oskar

AU - Ostertag, Lukas

AU - Mersdorf, Ulrike

AU - Platzman, Ilia

AU - Spatz, Joachim Pius

N1 - Funding Information: The authors acknowledge funding from the Federal Ministry of Education and Research of Germany, Grant Agreement no. 13XP5073A , PolyAntiBak and the MaxSynBio Consortium, the latter is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society . They also acknowledge the support from the Volkswagen Stiftung (priority call ‘Life?‘), the German Science Foundation SFB 1129 and the Deutsche Forschungsgemeinschaft ( DFG , German Research Foundation) under Germany's Excellence Strategy via the Excellence Cluster 3D Matter Made to Order ( EXC-2082/1–390761711 ). The authors are grateful to Julia Ricken for production and purification of recombinant GFP. J.P.S. acknowledge funding from the Gottfried Wilhelm Leibniz Award. J.E.H.B is grateful to Prof. Johannes Herrmann (Technical University of Kaiserslautern , Germany) for continuous support and critical discussion of the data. J.E.H.B. and O.S. acknowledge support from the Heidelberg Biosciences International Graduate School. O.S. acknowledges support from the Max Planck School Matter to Life and the Joachim Herz Foundation (add-on fellowship). O.S. is the Meurer Visiting Professor at the Max Planck Center for Minimal Biology, Bristol. The Max Planck Society is appreciated for its general support. Publisher Copyright: © 2022 The Authors

PY - 2022/4/13

Y1 - 2022/4/13

N2 - Immune vigilance ensures body integrity by eliminating malignant cells through the complex but coordinated cooperation of highly diversified lymphocytes populations. The sheer complexity of the immune system has slowed development of immunotherapies based on top-down genetic engineering of lymphocytes. In contrast, bottom-up assembly of synthetic cell compartments has contributed novel engineering strategies to reverse engineer and understand cellular phenomena as molecularly defined systems. Towards reducing the complexity of immunological systems, herein, a bottom-up approach for controlled assembly of fully-synthetic immune-inspired cells from predefined molecular components based on giant unilamellar vesicles is described. For construction of target-specific cytotoxic immune cells, the Fas-ligand-based apoptosis-inducing immune cell module is combined with an antibody-mediated cellular cytotoxicity-inspired system. The designed immune cells identify leukemia cells by specific surface antigens. Subsequently, they form stable attachments sites and eliminate their targets by induction of apoptosis. A structural and functional characterization of the synthetic immune cells by means of microfluidics, live cell, confocal and electron microscopy, dynamic light scattering as well as flow cytometry is presented. This study demonstrates the bioinspired construction of effector immune cells from defined molecular building blocks, enabling learning-by-building approaches in synthetic immunology.

AB - Immune vigilance ensures body integrity by eliminating malignant cells through the complex but coordinated cooperation of highly diversified lymphocytes populations. The sheer complexity of the immune system has slowed development of immunotherapies based on top-down genetic engineering of lymphocytes. In contrast, bottom-up assembly of synthetic cell compartments has contributed novel engineering strategies to reverse engineer and understand cellular phenomena as molecularly defined systems. Towards reducing the complexity of immunological systems, herein, a bottom-up approach for controlled assembly of fully-synthetic immune-inspired cells from predefined molecular components based on giant unilamellar vesicles is described. For construction of target-specific cytotoxic immune cells, the Fas-ligand-based apoptosis-inducing immune cell module is combined with an antibody-mediated cellular cytotoxicity-inspired system. The designed immune cells identify leukemia cells by specific surface antigens. Subsequently, they form stable attachments sites and eliminate their targets by induction of apoptosis. A structural and functional characterization of the synthetic immune cells by means of microfluidics, live cell, confocal and electron microscopy, dynamic light scattering as well as flow cytometry is presented. This study demonstrates the bioinspired construction of effector immune cells from defined molecular building blocks, enabling learning-by-building approaches in synthetic immunology.

U2 - 10.1016/j.biomaterials.2022.121522

DO - 10.1016/j.biomaterials.2022.121522

M3 - Article (Academic Journal)

C2 - 35500392

SN - 0142-9612

VL - 285

JO - Biomaterials

JF - Biomaterials

M1 - 121522

ER -

Bottom-up assembly of target-specific cytotoxic synthetic cells

Abstract

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