Synthetic living machines: A new window on life

Ebrahimkhani, Mo R.; Levin, Michael

doi:10.1016/j.isci.2021.102505

Cited by 42 publications

(35 citation statements)

References 199 publications

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“…Moreover, a wide range of novel organisms including cyborgs, hybrots, biobots, and others are being created by chimeric approaches that combine evolved and designed material. These efforts give rise to beings that cannot be placed within the natural phylogenetic tree of Earth, with behavioral competencies that cannot be readily guessed by analogy to familiar forms selected within specific environments [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Competency in Navigating Arbitrary Spaces as an Invariant for Analyzing Cognition in Diverse Embodiments

Fields

Levin

2022

Entropy

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113

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One of the most salient features of life is its capacity to handle novelty and namely to thrive and adapt to new circumstances and changes in both the environment and internal components. An understanding of this capacity is central to several fields: the evolution of form and function, the design of effective strategies for biomedicine, and the creation of novel life forms via chimeric and bioengineering technologies. Here, we review instructive examples of living organisms solving diverse problems and propose competent navigation in arbitrary spaces as an invariant for thinking about the scaling of cognition during evolution. We argue that our innate capacity to recognize agency and intelligence in unfamiliar guises lags far behind our ability to detect it in familiar behavioral contexts. The multi-scale competency of life is essential to adaptive function, potentiating evolution and providing strategies for top-down control (not micromanagement) to address complex disease and injury. We propose an observer-focused viewpoint that is agnostic about scale and implementation, illustrating how evolution pivoted similar strategies to explore and exploit metabolic, transcriptional, morphological, and finally 3D motion spaces. By generalizing the concept of behavior, we gain novel perspectives on evolution, strategies for system-level biomedical interventions, and the construction of bioengineered intelligences. This framework is a first step toward relating to intelligence in highly unfamiliar embodiments, which will be essential for progress in artificial intelligence and regenerative medicine and for thriving in a world increasingly populated by synthetic, bio-robotic, and hybrid beings.

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Section: Introductionmentioning

confidence: 99%

Competency in Navigating Arbitrary Spaces as an Invariant for Analyzing Cognition in Diverse Embodiments

Fields

Levin

2022

Entropy

Self Cite

113

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“…In summary, the pro-tumorigenic or inhibitor roles of particular gap junctions suggests context-dependent therapeutic actions based on the transcriptional control of specific connexin levels together with the postranslational modification of the junction function using inhibitors and blockers [ 14 , 32 , 33 , 34 ]. These results can also be relevant to the design of synthetic bioelectric systems, whether in vitro [ 12 , 53 ] or in vivo [ 54 ]. The problems to be faced in practical applications are the variety of bioelectrical responses that can be obtained as a function of the connexin type, intercellular coupling degree, and patch size, as shown in Figure 3 , Figure 4 , Figure 5 and Figure 6 .…”

Section: Resultsmentioning

confidence: 99%

Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate

Riol

Cervera

Levin

et al. 2021

Cancers

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Electric potential distributions can act as instructive pre-patterns for development, regeneration, and tumorigenesis in cell systems. The biophysical states influence transcription, proliferation, cell shape, migration, and differentiation through biochemical and biomechanical downstream transduction processes. A major knowledge gap is the origin of spatial patterns in vivo, and their relationship to the ion channels and the electrical synapses known as gap junctions. Understanding this is critical for basic evolutionary developmental biology as well as for regenerative medicine. We computationally show that cells may express connexin proteins with different voltage-gated gap junction conductances as a way to maintain multicellular regions at distinct membrane potentials. We show that increasing the multicellular connectivity via enhanced junction function does not always contribute to the bioelectrical normalization of abnormally depolarized multicellular patches. From a purely electrical junction view, this result suggests that the reduction rather than the increase of specific connexin levels can also be a suitable bioelectrical approach in some cases and time stages. We offer a minimum model that incorporates effective conductances ultimately related to specific ion channel and junction proteins that are amenable to external regulation. We suggest that the bioelectrical patterns and their encoded instructive information can be externally modulated by acting on the mean fields of cell systems, a complementary approach to that of acting on the molecular characteristics of individual cells. We believe that despite the limitations of a biophysically focused model, our approach can offer useful qualitative insights into the collective dynamics of cell system bioelectricity.

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“…Although iPSCs ensure histocompatibility and avoid ethical conflicts, tumor formation remains unresolved. Recently, iPSCs have been shown to produce self-organizing organoids with different cell types through genetic reprogramming or exposure to environmental signaling factors ( Ebrahimkhani and Levin, 2021 ). Gilpin et al evaluated the recellularization of decellularized lung scaffold with lung endothelial and epithelial progenitor cells derived from human iPSCs.…”

Section: Pre-application Processingmentioning

confidence: 99%

Decellularization in Tissue Engineering and Regenerative Medicine: Evaluation, Modification, and Application Methods

Neishabouri

Khaboushan

Daghigh

et al. 2022

Front. Bioeng. Biotechnol.

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Reproduction of different tissues using scaffolds and materials is a major element in regenerative medicine. The regeneration of whole organs with decellularized extracellular matrix (dECM) has remained a goal despite the use of these materials for different purposes. Recently, decellularization techniques have been widely used in producing scaffolds that are appropriate for regenerating damaged organs and may be able to overcome the shortage of donor organs. Decellularized ECM offers several advantages over synthetic compounds, including the preserved natural microenvironment features. Different decellularization methods have been developed, each of which is appropriate for removing cells from specific tissues under certain conditions. A variety of methods have been advanced for evaluating the decellularization process in terms of cell removal efficiency, tissue ultrastructure preservation, toxicity, biocompatibility, biodegradability, and mechanical resistance in order to enhance the efficacy of decellularization methods. Modification techniques improve the characteristics of decellularized scaffolds, making them available for the regeneration of damaged tissues. Moreover, modification of scaffolds makes them appropriate options for drug delivery, disease modeling, and improving stem cells growth and proliferation. However, considering different challenges in the way of decellularization methods and application of decellularized scaffolds, this field is constantly developing and progressively moving forward. This review has outlined recent decellularization and sterilization strategies, evaluation tests for efficient decellularization, materials processing, application, and challenges and future outlooks of decellularization in regenerative medicine and tissue engineering.

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Synthetic living machines: A new window on life

Cited by 42 publications

References 199 publications

Competency in Navigating Arbitrary Spaces as an Invariant for Analyzing Cognition in Diverse Embodiments

Competency in Navigating Arbitrary Spaces as an Invariant for Analyzing Cognition in Diverse Embodiments

Cell Systems Bioelectricity: How Different Intercellular Gap Junctions Could Regionalize a Multicellular Aggregate

Decellularization in Tissue Engineering and Regenerative Medicine: Evaluation, Modification, and Application Methods

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