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      Intercellular communication between artificial cells by allosteric amplification of a molecular signal

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          Abstract

          Multicellular organisms rely on intercellular communication to coordinate the behaviour of individual cells, which enables their differentiation and hierarchical organization. Various cell mimics have been developed to establish fundamental engineering principles for the construction of artificial cells displaying cell-like organization, behaviour and complexity. However, collective phenomena, although of great importance for a better understanding of life-like behaviour, are underexplored. Here, we construct collectives of giant vesicles that can communicate with each other through diffusing chemical signals that are recognized and processed by synthetic enzymatic cascades. Similar to biological cells, the Receiver vesicles can transduce a weak signal originating from Sender vesicles into a strong response by virtue of a signal amplification step, which facilitates the propagation of signals over long distances within the artificial cell consortia. This design advances the development of interconnected artificial cells that can exchange metabolic and positional information to coordinate their higher-order organization.

          Abstract

          The principles of intercellular communication in multicellular organisms can be explored using artificial cells. Here, the authors report on giant vesicles which can recognize diffused chemical signals and amplify the signal by synthetic enzymatic cascades to allow signal propagation over long distances.

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          Liposomes and polymersomes: a comparative review towards cell mimicking

          Minimal cells: we compare and contrast liposomes and polymersomes for a better a priori choice and design of vesicles and try to understand the advantages and shortcomings associated with using one or the other in many different aspects (properties, synthesis, self-assembly, applications). Cells are integral to all forms of life due to their compartmentalization by the plasma membrane. However, living organisms are immensely complex. Thus there is a need for simplified and controllable models of life for a deeper understanding of fundamental biological processes and man-made applications. This is where the bottom-up approach of synthetic biology comes from: a stepwise assembly of biomimetic functionalities ultimately into a protocell. A fundamental feature of such an endeavor is the generation and control of model membranes such as liposomes and polymersomes. We compare and contrast liposomes and polymersomes for a better a priori choice and design of vesicles and try to understand the advantages and shortcomings associated with using one or the other in many different aspects (properties, synthesis, self-assembly, applications) and which aspects have been studied and developed with each type and update the current development in the field.
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            A tissue-like printed material.

            Living cells communicate and cooperate to produce the emergent properties of tissues. Synthetic mimics of cells, such as liposomes, are typically incapable of cooperation and therefore cannot readily display sophisticated collective behavior. We printed tens of thousands of picoliter aqueous droplets that become joined by single lipid bilayers to form a cohesive material with cooperating compartments. Three-dimensional structures can be built with heterologous droplets in software-defined arrangements. The droplet networks can be functionalized with membrane proteins; for example, to allow rapid electrical communication along a specific path. The networks can also be programmed by osmolarity gradients to fold into otherwise unattainable designed structures. Printed droplet networks might be interfaced with tissues, used as tissue engineering substrates, or developed as mimics of living tissue.
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              Artificial Cells: Synthetic Compartments with Life-like Functionality and Adaptivity

              Conspectus Cells are highly advanced microreactors that form the basis of all life. Their fascinating complexity has inspired scientists to create analogs from synthetic and natural components using a bottom-up approach. The ultimate goal here is to assemble a fully man-made cell that displays functionality and adaptivity as advanced as that found in nature, which will not only provide insight into the fundamental processes in natural cells but also pave the way for new applications of such artificial cells. In this Account, we highlight our recent work and that of others on the construction of artificial cells. First, we will introduce the key features that characterize a living system; next, we will discuss how these have been imitated in artificial cells. First, compartmentalization is crucial to separate the inner chemical milieu from the external environment. Current state-of-the-art artificial cells comprise subcompartments to mimic the hierarchical architecture of eukaryotic cells and tissue. Furthermore, synthetic gene circuits have been used to encode genetic information that creates complex behavior like pulses or feedback. Additionally, artificial cells have to reproduce to maintain a population. Controlled growth and fission of synthetic compartments have been demonstrated, but the extensive regulation of cell division in nature is still unmatched. Here, we also point out important challenges the field needs to overcome to realize its full potential. As artificial cells integrate increasing orders of functionality, maintaining a supporting metabolism that can regenerate key metabolites becomes crucial. Furthermore, life does not operate in isolation. Natural cells constantly sense their environment, exchange (chemical) signals, and can move toward a chemoattractant. Here, we specifically explore recent efforts to reproduce such adaptivity in artificial cells. For instance, synthetic compartments have been produced that can recruit proteins to the membrane upon an external stimulus or modulate their membrane composition and permeability to control their interaction with the environment. A next step would be the communication of artificial cells with either bacteria or another artificial cell. Indeed, examples of such primitive chemical signaling are presented. Finally, motility is important for many organisms and has, therefore, also been pursued in synthetic systems. Synthetic compartments that were designed to move in a directed, controlled manner have been assembled, and directed movement toward a chemical attractant is among one of the most life-like directions currently under research. Although the bottom-up construction of an artificial cell that can be truly considered “alive” is still an ambitious goal, the recent work discussed in this Account shows that this is an active field with contributions from diverse disciplines like materials chemistry and biochemistry. Notably, research during the past decade has already provided valuable insights into complex synthetic systems with life-like properties. In the future, artificial cells are thought to contribute to an increased understanding of processes in natural cells and provide opportunities to create smart, autonomous, cell-like materials.
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                Author and article information

                Contributors
                j.c.m.v.hest@tue.nl
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                3 April 2020
                3 April 2020
                2020
                : 11
                : 1652
                Affiliations
                [1 ]ISNI 0000 0004 0398 8763, GRID grid.6852.9, Department of Chemical Engineering and Chemistry, , Eindhoven University of Technology, ; PO Box 513, 5600 MB Eindhoven, the Netherlands
                [2 ]ISNI 0000 0004 0398 8763, GRID grid.6852.9, Institute for Complex Molecular Systems, Eindhoven University of Technology, ; PO Box 513, 5600 MB Eindhoven, the Netherlands
                [3 ]ISNI 0000000122931605, GRID grid.5590.9, Radboud University, ; PO Box 9102, 6500 HC Nijmegen, the Netherlands
                [4 ]ISNI 0000 0004 0398 8763, GRID grid.6852.9, Department of Biomedical Engineering, , Eindhoven University of Technology, ; PO Box 513, 5600 MB Eindhoven, the Netherlands
                Author information
                http://orcid.org/0000-0002-4819-9499
                http://orcid.org/0000-0001-7973-2404
                Article
                15482
                10.1038/s41467-020-15482-8
                7125153
                32246068
                47132cae-4725-4ca3-ba0f-9281c84a69f6
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 8 January 2020
                : 13 March 2020
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                © The Author(s) 2020

                Uncategorized
                origin of life,molecular capsules,other nanotechnology
                Uncategorized
                origin of life, molecular capsules, other nanotechnology

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