Fig 4 - uploaded by Lev Beloussov
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Active extension response to the over-threshold stretching of an epithelial sheet. A) General scheme. Strong enough tangential contraction of the left part cells may induce the active extension of the right part cells (double-head arrows) associated with convergent movements of laterally located cells (oblique arrows). B) Trajectories of cell movements in explants of Xenopus embryonic ectoderm stretched in horizontal direction, traced within first 20 min after the end of stretching. C)-E) Experimental testing of TIAE. C) is a non-stretched sample.
Source publication
A deep (although at the first glance naïve) question which may be addressed to embryonic development is why during this process quite definite and accurately reproduced successions of precise and complicated shapes are taking place, or why, in several cases, the result of development is highly precise in spite of an extensive variability of interme...
Contexts in source publication
Context 1
... are taken ad hoc. Also, as shown experimentally, the segregation of a cell layer into columnar and flattened domains is followed by the generation of active pressure stresses within the flattened domain, the pressure force being oriented in the previous tension direction [14]. We define this value as the tension-induced active extension (TIAE) ( fig. 4A-F). A wide-spread example of TIAE is a so-called "convergent cell intercalation" ...
Context 2
... main results of circular shape modeling are plot- ted within the W/N coordinates of morphospace ( fig. 14). This graph is subdivided into oblique zones with station- ary shapes (empty) that are alternated by areas occupied by asymmetric and unstable shapes (filled). The number of lobes in each of the stable shapes is smaller than the corre- sponding N value. Hence, in all cases, the symmetry order of the obtained figures is reduced in ...
Citations
... We first investigated aspects of regulatory network structure tuned to cell jamming-a ubiquitous transition between liquid-like and solid-like physical phases where homogeneous cell groups spontaneously form and dissolve small islands of densely packed ("caged") slow-moving cells [57][58][59][60] . Although this transition is an essential feature of early multicellular development, it is invariant to local adaptations and exemplifies the most basic integration of physical processes driving jamming with biological processes by which cells modulate them [61][62][63] . Consequently, network features enabling cell jamming transitions reflect the continuity of early embryonic development prior to the onset of tissue differentiation and modification. ...
Development and evolution require both stability and adaptability, yet how these opposite properties are reconciled is unclear. Here, we show that intrinsically disordered proteins (IDPs) act as reset mechanisms in conserved regulatory networks facilitating developmental transitions by integrating physical processes with genetic regulation. By tracing the ontogeny of mesenchymal cells in avian beak primordia, we demonstrate that mechanosensitive IDPs mediate shifts between physical cell states via dosage-dependent binding plasticity, converting stochastic protein variation into discreet regulatory networks. The disorder-enabled connectivity in these proteins resets their regulatory specialization and promotes population divergence. Comparative analyses across avian proteomes confirm that binding plasticity in transcriptional IDPs drives their diverse regulatory associations and accelerates their evolution. By resetting specialized states in conserved regulatory networks, IDPs flexibly regulate developmental pathways and reconcile precision with evolvability.
... Morphomechanics is an approach to the study of morphogenesis in living systems that, contrarily to the genetic -or bioelectric -program for development, is formulated on the idea of living matter as an active medium (Beloussov 2002;Beloussov 2008;Beloussov 2012b). In the present work, it is shown that morphomechanics: 1) is supported by recent findings in active liquid crystals, 2) can integrate bioelectrical signals as the mechanism by which cells measure mechanical stress, 3) in combination with the differentiation waves, can be extended to integrate cell differentiation. ...
... Here it is important to stress that, according to Beloussov (2008;2012a), the hyper-restoration response is not specifically biological (i.e. arbitrary), but it can be understood as the extension of the Le Chatelier principle for active matter (i.e., at far from equilibrium conditions). ...
Morphomechanics is based on the idea that living matter can mechanically self-organize into forms without the need for a pre-pattern, as recently supported by the physics of active matter. Here an extended view is proposed that integrates bioelectricity and differentiation waves as the mechanisms by which cells measure mechanical stress and couple morphogenesis and cell differentiation, respectively. Morphomechanics is a largely unexplored approach, which however could deeply transform our way of seeing nature.
... Morphomechanics is an approach to the study of morphogenesis in living systems that, contrarily to the genetic -or bioelectric -program for development, is formulated on the idea of living matter as an active medium (Beloussov 2002;Beloussov 2008;Beloussov 2012b). In the present work, it is shown that morphomechanics: 1) is supported by recent findings in active liquid crystals, 2) can integrate bioelectrical signals as the mechanism by which cells measure mechanical stress, 3) in combination with the differentiation waves, can be extended to integrate cell differentiation. ...
... Here it is important to stress that, according to Beloussov (2008;2012a), the hyper-restoration response is not specifically biological (i.e. arbitrary), but it can be understood as the extension of the Le Chatelier principle for active matter (i.e., at far from equilibrium conditions). ...
Morphomechanics is based on the idea that living matter can mechanically self-organize into forms without the need for a pre-pattern, as recently supported by the physics of active matter. Here an extended view is proposed that integrates bioelectricity and differentiation waves as the mechanisms by which cells measure mechanical stress and couple morphogenesis and cell differentiation, respectively. Morphomechanics is a largely unexplored approach, which however could deeply transform our way of seeing nature.
... Il locus of control è una disposizione mentale che indica se si attribuisce o no il controllo della vita a cause esterne o interne4 Il concetto di coping -traducibile letteralmente dall'inglese con "far fronte", "fronteggiare", "tenere testa" -è impiegato in psicologia per indicare una serie di comportamenti messi in atto dagli individui per cercare di tenere sotto controllo, affrontare e/o minimizzare conflitti e situazioni o eventi stressanti ...
Scopo di questo articolo è quello di porre attenzione sulla possibilità reale che l’origine del cancro sia di tipo Psiche-Somatica1 e che quindi sia legata al collasso energetico/elettromagnetico delle informazioni legate all’esperienza traumatica e che poi si abbia come conseguenza una proliferazione non controllata di cellule che hanno la capacità poi di infiltrarsi nei normali organi e tessuti dell’organismo alterandone la struttura e il funzionamento. Attraverso le conoscenze attuali della Biofisica Informazionale si porrà quindi attenzione sulla possibilità che il cancro abbia una differente origine da quelle che in campo medico attualmente lo vedono come causato da mutazioni del DNA all’interno delle cellule. Il DNA cellulare contiene informazioni su come le cellule debbano crescere e moltiplicarsi. Secondo questa teoria vi sono errori in queste istruzioni che fanno in modo che la cellula diventi cancerosa.
... Here it is important to stress that, according to Beloussov (2008;2012a), the hyper-restoration response is not specifically biological (i.e. arbitrary), but it can be understood as the extension of the Le Chatelier principle for active matter (i.e., at far from equilibrium conditions). ...
Morphomechanics is based on the idea that living matter can mechanically self-organize into forms without the need for a pre-pattern, as recently supported by the physics of active matter. Here an extended view is proposed that integrates bioelectricity and differentiation waves as the mechanisms by which cells measure mechanical stress and couple morphogenesis and cell differentiation, respectively. Morphomechanics is a largely unexplored approach, which however could deeply transform our way of seeing nature.
... As shown by tracing immediate mechanical reactions of the incised tissues, the head region of the neuroectoderm is compressed along the anteroposterior axis, whereas the trunk region of the neuroectoderm is stretched along this axis [15,16]. This finding indirectly suggests that if MTs do indeed play a role in regulatory signaling, they may specify different types of cell differentiation in the trunk and head regions of the neural anlage. ...
During gastrulation and neurulation, the chordamesoderm and overlying neuroectoderm of vertebrate embryos converge under the control of a specific genetic programme to the dorsal midline, simultaneously extending along it. However, whether mechanical tensions resulting from these morphogenetic movements play a role in long-range feedback signaling that in turn regulates gene expression in the chordamesoderm and neuroectoderm is unclear. In the present work, by using a model of artificially stretched explants of Xenopus midgastrula embryos and full-transcriptome sequencing, we identified genes with altered expression in response to external mechanical stretching. Importantly, mechanically activated genes appeared to be expressed during normal development in the trunk, i.e., in the stretched region only. By contrast, genes inhibited by mechanical stretching were normally expressed in the anterior neuroectoderm, where mechanical stress is low. These results indicate that mechanical tensions may play the role of a long-range signaling factor that regulates patterning of the embryo, serving as a link coupling morphogenesis and cell differentiation.
... The principle of increased external work formulated by Bauer to explain complexification processes in the course of evolution as related to the process of hyper-restoration was suggested by Lev Beloussov for the explanation of morphogenetic phenomena. The hyper-restoring feedback loops drive complexification in the course of individual development (Beloussov 2008(Beloussov , 2012. According to Beloussov, the generation of form in the course of the development of a multicellular organism occurs not via a simple relaxation to the previous state but through a hyper-relaxation leading to further hyper-restoration that provides accumulation of additional energy to make extra work in the next cycle of morphogenesis (Beloussov and Luchinskaia, 1995;Beloussov, 2008Beloussov, , 2012. ...
... The hyper-restoring feedback loops drive complexification in the course of individual development (Beloussov 2008(Beloussov , 2012. According to Beloussov, the generation of form in the course of the development of a multicellular organism occurs not via a simple relaxation to the previous state but through a hyper-relaxation leading to further hyper-restoration that provides accumulation of additional energy to make extra work in the next cycle of morphogenesis (Beloussov and Luchinskaia, 1995;Beloussov, 2008Beloussov, , 2012. ...
... Xenobots suggest the existence of analogous 'not-natural attractors' in morphospace (behaviour space) 85,86 . A better understanding of how these arise, and of their relationship to attractors in normal development, as well as 'generic' laws to define the space of possibilities [87][88][89] , will be important to explain the origin of xenobots [73][74][75] and many other possible constructs that remain to be discovered. Second, it needs to be understood how evolution creates genomes that do not encode solutions to specific environments, but rather seed the production of highly competent 'machines' that can solve numerous new problems 90 . ...
Bioengineering can address many important needs, from transformative biomedicine to environmental remediation. In addition to practical applications, the construction of new living systems will increase our understanding of biology and will nurture emerging intersections between biological and computational sciences. In this Review, we discuss the transition from cell-level synthetic biology to multicellular synthetic morphology. We highlight experimental embryology studies, including organoids and xenobots, that go beyond the familiar, default outcomes of embryogenesis, revealing the plasticity, interoperability and problem-solving capacities of life. In addition to traditional bottom-up engineering of genes and proteins, design strategies can be pursued based on modelling cell collectives as agential materials, with their own goals, agendas and powers of problem-solving. Such an agential bioengineering approach could transform developmental biology, regenerative medicine and robotics, building on frameworks that include active, computational and agential matter. Synthetic morphogenesis is limited by knowledge gaps about the competencies of cells and cell groups. This Review discusses a synthetic bioengineering framework based on empirically determined properties of cells, including goal-seeking and agential behaviours, which will allow the creation of complex devices that cannot be built using bottom-up approaches. Synthetic bioengineering allows the construction of new arrangements of living material.Synthetic morphology aims at creating an ‘anatomical compiler’ that writes DNA instructions based on a specific design goal.Bottom-up bioengineering approaches are limited by knowledge gaps in developmental biology, thus relying on the micromanagement of passive materials.Cells and tissues are effectively manipulated as agential materials, by targeting their pattern memory and homeostatic capabilities.Extending bottom-up approaches by adding empirically and computationally characterized agential materials (cells and tissues) will greatly improve the rational creation and repair of complex morphologies. Synthetic bioengineering allows the construction of new arrangements of living material. Synthetic morphology aims at creating an ‘anatomical compiler’ that writes DNA instructions based on a specific design goal. Bottom-up bioengineering approaches are limited by knowledge gaps in developmental biology, thus relying on the micromanagement of passive materials. Cells and tissues are effectively manipulated as agential materials, by targeting their pattern memory and homeostatic capabilities. Extending bottom-up approaches by adding empirically and computationally characterized agential materials (cells and tissues) will greatly improve the rational creation and repair of complex morphologies.
... During development, organisms emerge as the result of a complex set of interactions among cells, with anatomical order and functionality being the result of cellular activities. While genomes specify the cellular hardware (proteins), it is the software (cellular activity) studied by developmental biologists that is ultimately responsible for the organism's overall structure and behavior [14][15][16][17][18]. ...
Biological genotypes do not code directly for phenotypes; developmental physiology is the control layer that separates genomes from capacities ascertained by selection. A key aspect is cellular competency, since cells are not passive materials but descendants of unicellular organisms with complex context-sensitive behavioral capabilities. To probe the effects of different degrees of cellular competency on evolutionary dynamics, we used an evolutionary simulation in the context of minimal artificial embryogeny. Virtual embryos consisted of a single axis of positional information values provided by cells’ ‘structural genes’, operated upon by an evolutionary cycle in which embryos’ fitness was proportional to monotonicity of the axial gradient. Evolutionary dynamics were evaluated in two modes: hardwired development (genotype directly encodes phenotype), and a more realistic mode in which cells interact prior to evaluation by the fitness function (“regulative” development). We find that even minimal ability of cells with to improve their position in the embryo results in better performance of the evolutionary search. Crucially, we observed that increasing the behavioral competency masks the raw fitness encoded by structural genes, with selection favoring improvements to its developmental problem-solving capacities over improvements to its structural genome. This suggests the existence of a powerful ratchet mechanism: evolution progressively becomes locked in to improvements in the intelligence of its agential substrate, with reduced pressure on the structural genome. This kind of feedback loop in which evolution increasingly puts more effort into the developmental software than perfecting the hardware explains the very puzzling divergence of genome from anatomy in species like planaria. In addition, it identifies a possible driver for scaling intelligence over evolutionary time, and suggests strategies for engineering novel systems in silico and in bioengineering.
... However, Xenobots' linear behavior consistency was not as high (67%) when compared to Anthrobots (80%). Despite their highly divergent genome, age, and tissue origin, the two platforms assemble into very similar types of creatures, illustrating the importance of generic laws of morphogenesis 8,[68][69][70][71][72] in addition to species-specific genomic information. ...
Fundamental knowledge gaps exist with respect to the plasticity of cells from adult soma and the potential diversity of body shape and behavior in living constructs derived from such genetically wild-type cells. Here we introduce Anthrobots, a spheroid-shaped multicellular biological robot (biobot) platform with diameters ranging from 30 to 500 microns. Anthrobots have an inherent capacity for motility in aqueous environments, via cilia covering their surface. Each Anthrobot starts out as a single cell, derived from the adult human lung, and self-constructs into a multicellular motile biobot after having been cultured in extra cellular matrix for 2 weeks and transferred into a minimally viscous habitat. Anthrobots exhibit a wide range of behaviors with motility patterns ranging from tight loops to straight lines and speeds ranging from 5-50 microns/second. Our anatomical investigations reveal that this behavioral diversity is significantly correlated with their morphological diversity. Anthrobots can assume diverse morphologies from fully polarized to wholly ciliated bodies with spherical or ellipsoidal shapes, each correlating with a distinct movement type. Remarkably, as a function of these different movement types, Anthrobots were found to be capable of traversing live human tissues in various ways. Furthermore, Anthrobots were able to induce rapid repair of wounds in human neural cell sheets in vitro. By controlling microenvironmental cues in bulk, entirely novel structure, behavior, and biomedically-relevant capabilities can be discovered in morphogenetic processes without direct genetic editing or manual sculpting.
Significance Statement
We demonstrate that normal, non-genetically-modified human tracheal cells can be induced to form a new proto-organism - Anthrobots - which exhibit spontaneous behavior, swimming around in one of several patterns, demonstrating plasticity for novel form and function inherent in even elderly human somatic cells. Moreover, Anthrobots are able to traverse over cultured neurons, settling down and causing repair under them: the nerves knit together across the wound gap due to the presence of the Anthrobot. A patient’s own cells can be harnessed to make a motile biological robot that can traverse human tissue and induce repair. In the future, this platform can deliver pro-regenerative therapeutics for a range of biomedical applications that will not trigger rejection or require immune suppression.
