scholarly journals On the evolution and development of morphological complexity: A view from gene regulatory networks

2021 ◽  
Vol 17 (2) ◽  
pp. e1008570
Author(s):  
Pascal F. Hagolani ◽  
Roland Zimm ◽  
Renske Vroomans ◽  
Isaac Salazar-Ciudad
Keyword(s):  
Gene Networks ◽  
Animal Cell ◽  
Random Network ◽  
Random Search ◽  
Single Cells ◽  
Cell Behaviors ◽  
Morphological Complexity ◽  
Specific Distribution ◽  
Phenotypic Complexity ◽  
Robust To Noise

How does morphological complexity evolve? This study suggests that the likelihood of mutations increasing phenotypic complexity becomes smaller when the phenotype itself is complex. In addition, the complexity of the genotype-phenotype map (GPM) also increases with the phenotypic complexity. We show that complex GPMs and the above mutational asymmetry are inevitable consequences of how genes need to be wired in order to build complex and robust phenotypes during development.We randomly wired genes and cell behaviors into networks in EmbryoMaker. EmbryoMaker is a mathematical model of development that can simulate any gene network, all animal cell behaviors (division, adhesion, apoptosis, etc.), cell signaling, cell and tissues biophysics, and the regulation of those behaviors by gene products. Through EmbryoMaker we simulated how each random network regulates development and the resulting morphology (i.e. a specific distribution of cells and gene expression in 3D). This way we obtained a zoo of possible 3D morphologies. Real gene networks are not random, but a random search allows a relatively unbiased exploration of what is needed to develop complex robust morphologies. Compared to the networks leading to simple morphologies, the networks leading to complex morphologies have the following in common: 1) They are rarer; 2) They need to be finely tuned; 3) Mutations in them tend to decrease morphological complexity; 4) They are less robust to noise; and 5) They have more complex GPMs. These results imply that, when complexity evolves, it does so at a progressively decreasing rate over generations. This is because as morphological complexity increases, the likelihood of mutations increasing complexity decreases, morphologies become less robust to noise, and the GPM becomes more complex. We find some properties in common, but also some important differences, with non-developmental GPM models (e.g. RNA, protein and gene networks in single cells).

scholarly journals Cell signalling stabilizes morphogenesis against noise

2019 ◽  
Author(s):  
Pascal Hagolani ◽  
Roland Zimm ◽  
Miquel Marin-Riera ◽  
Isaac Salazar-Ciudad
Keyword(s):  
Cell Division ◽  
Gene Networks ◽  
Cell Signalling ◽  
Huge Number ◽  
Cell Behaviors ◽  
Animal Development ◽  
Extracellular Signaling ◽  
General Mathematical Model ◽  
Robust To Noise ◽  
Early Metazoan

AbstractEmbryonic development involves gene networks, extracellular signaling, cell behaviors (cell division, apoptosis, adhesion, etc.) and mechanical interactions. How should gene networks, extracellular signaling and cell behaviors be coordinated to lead to complex and robust morphologies?To explore this question, we randomly wired genes and cell behaviors into a huge number of networks in EmbryoMaker. EmbryoMaker is a general mathematical model of animal development that simulates how embryos change,i.e.how the 3D spatial position of cells change, over time due such networks. Real gene networks are not random. Random networks, however, allow an unbiased view on the requirements for complex and robust development.We found that the mere autonomous activation of cell behaviors, especially cell division and contraction, was able to lead to the development of complex morphologies. We also found that complex morphologies tend to be less robust to noise than simple morphologies. However, we found that morphologies that developed through extracellular signaling and complex gene networks were, on average, more robust to noise. This stabilization occurs when gene networks and extracellular signaling partition the embryo into different regions where cell behaviors are regulated in slightly different ways. Our results are consistent with theories proposing that morphological complexity arose in early metazoan evolution as a consequence of the cell bio-mechanics already present in protozoa and that robustness evolved by the co-option of gene networks and extracellular cell signaling.

scholarly journals Randomly connected networks generate emergent selectivity and predict decoding properties of large populations of neurons

2019 ◽  
Author(s):  
Audrey Sederberg ◽  
Ilya Nemenman
Keyword(s):  
Cortical Neurons ◽  
Posterior Parietal Cortex ◽  
Neural Circuit ◽  
Functional Organization ◽  
Alternative Hypothesis ◽  
Random Network ◽  
Single Cells ◽  
Emergent Properties ◽  
Alternative Mechanism ◽  
Large Populations

AbstractAdvances in neural recording methods enable sampling from populations of thousands of neurons during the performance of behavioral tasks, raising the question of how recorded activity relates to the theoretical models of computations underlying performance. In the context of decision making in rodents, patterns of functional connectivity between choice-selective cortical neurons, as well as broadly distributed choice information in both excitatory and inhibitory populations, were recently reported [1]. The straightforward interpretation of these data suggests a mechanism relying on specific patterns of anatomical connectivity to achieve selective pools of inhibitory as well as excitatory neurons. We investigate an alternative mechanism for the emergence of these experimental observations using a computational approach. We find that a randomly connected network of excitatory and inhibitory neurons generates single-cell selectivity, patterns of pairwise correlations, and indistinguishable excitatory and inhibitory readout weight distributions, as observed in recorded neural populations. Further, we make the readily verifiable experimental predictions that, for this type of evidence accumulation task, there are no anatomically defined sub-populations of neurons representing choice, and that choice preference of a particular neuron changes with the details of the task. This work suggests that distributed stimulus selectivity and patterns of functional organization in population codes could be emergent properties of randomly connected networks.Author summaryWhat can we learn about neural circuit organization and function from recordings of large populations of neurons? For example, in population recordings in the posterior parietal cortex of mice performing an evidence integration task, particular patterns of selectivity and correlations between cells were observed. One hypothesis for an underlying mechanism generating these patterns is that they follow from intricate rules of connectivity between specific neurons, but this raises the question of how such intricate patterns arise during learning or development. An alternative hypothesis, which we explore here, is that such patterns emerge from networks with broad spectra of eigenvalues, which is a generic property of certain random networks. We find that a random network model matches many features of experimental recordings, from single cells to populations. We suggest that such emergent selectivity could be an important principle in brain areas, in which a broad distribution of selectivity is observed.

scholarly journals Single-cell intracellular pH measurements reveal cell-cycle linked pH dynamics

2021 ◽  
Author(s):  
Julia S Spear ◽  
Katharine A White
Keyword(s):  
Cell Cycle ◽  
Single Cell ◽  
Intracellular Ph ◽  
Cell Cycle Progression ◽  
Single Cells ◽  
Population Level ◽  
Growth Factor Signaling ◽  
Cycle Progression ◽  
Cell Behaviors ◽  
Sinusoidal Pattern

Transient changes in intracellular pH (pHi) have been shown to regulate normal cell behaviors like migration and cell-cycle progression, while dysregulated pHi dynamics are a hallmark of cancer. However, little is known about how pHi heterogeneity and dynamics influence population-level measurements or single-cell behaviors. Here, we present and characterize single-cell pHi heterogeneity distributions in both normal and cancer cells and measure dynamic pHi increases in single cells in response to growth factor signaling. Next, we measure pHi dynamics in single cells during cell cycle progression. We determined that single-cell pHi is significantly decreased at the G1/S boundary, increases from S phase to the G2/M transition, rapidly acidifies during mitosis, and recovers in daughter cells. This sinusoidal pattern of pHi dynamics was linked to cell cycle timing regardless of synchronization method. This work confirms prior work at the population level and reveals distinct advantages of single-cell pHi measurements in capturing pHi heterogeneity across a population and dynamics within single cells.

scholarly journals Cell behaviors within a confined adhesive area fabricated using novel micropatterning methods

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262632
Author(s):  
Tsukasa Nakatoh ◽  
Takuji Osaki ◽  
Sohma Tanimoto ◽  
Md. Golam Sarowar Jahan ◽  
Tomohisa Kawakami ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Division ◽  
Single Cells ◽  
Cell Behavior ◽  
Air Plasma ◽  
Cell Behaviors ◽  
Laser Ablation Method ◽  
Increasing Demand ◽  
Division Cell ◽  
Adhesive Coating

In the field of cell and tissue engineering, there is an increasing demand for techniques to spatially control the adhesion of cells to substrates of desired sizes and shapes. Here, we describe two novel methods for fabricating a substrate for adhesion of cells to a defined area. In the first method, the surface of the coverslip or plastic dish was coated with Lipidure, a non-adhesive coating material, and air plasma was applied through a mask with holes, to confer adhesiveness to the surface. In the second method, after the surface of the coverslip was coated with gold by sputtering and then with Lipidure; the Lipidure coat was locally removed using a novel scanning laser ablation method. These methods efficiently confined cells within the adhesive area and enabled us to follow individual cells for a longer duration, compared to the currently available commercial substrates. By following single cells within the confined area, we were able to observe several new aspects of cell behavior in terms of cell division, cell–cell collisions, and cell collision with the boundary between adhesive and non-adhesive areas.

scholarly journals Mapping Surface Charge Distribution of Single-Cell via Charged Nanoparticle

2021 ◽  
Author(s):  
Leixin Ouyang ◽  
Rubia Shaik ◽  
Ruiting Xu ◽  
Ge Zhang ◽  
Jiang Zhe
Keyword(s):  
Cell Surface ◽  
Charge Density ◽  
Surface Charge ◽  
Charge Distribution ◽  
Surface Charge Density ◽  
Single Cells ◽  
Cell Behaviors ◽  
Cell Surface Charge ◽  
Surface Charge Distribution ◽  
Fluorescence Light

Abstract Background: Many bio-functions of cells can be regulated by their surface charge characteristics. Mapping surface charge density in a single cell’s surface is vital to advance the understanding of cell behaviors. Results: This article demonstrates a method of cell surface charge mapping via electrostatic cell–nanoparticle interactions. Nanoparticles with fluorescence were used as the marker to investigate single cells’ surface charge distribution. The nanoparticles with opposite charges were electrostatically bonded to the cell surface; a stack of fluorescence distribution on a cell’s surface at a series of vertical distances was imaged and analyzed. By establishing a relationship between fluorescence light intensity and surface charge density, cells’ surface charge distribution was quantified from the fluorescence distribution. Two types of cells, HUVECs and Hela cells, were tested. From the measured surface charge density of a group of single cells, the average zeta potential of the two types of cells was obtained, which is in good agreement with the standard electrophoretic light scattering measurement. Conclusions: This method can be used for rapid surface charge mapping of single particles or cells and can advance cell-surface-charge characterization applications in many biomedical fields.

scholarly journals A new approach to design artificial 3D micro-niches with combined chemical, topographical and rheological cues

2018 ◽  
Author(s):  
Celine Stoecklin ◽  
Zhang Yue ◽  
Wilhelm W. Chen ◽  
Richard de Mets ◽  
Eileen Fong ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Single Cells ◽  
Specific Property ◽  
Biological Response ◽  
Environmental Cues ◽  
Protein Patterns ◽  
Cell Behaviors ◽  
Photoactive Materials ◽  
Bona Fide

AbstractThe in vitro methods to recapitulate environmental cues around cells are usually optimized to test a specific property of the environment (biochemical nature or the stiffness of the extra cellular matrix (ECM), or nanotopography) for its capability to induce defined cell behaviors (lineage commitment, migration). Approaches that combine different environmental cues in 3D to assess the biological response of cells to the spatial organization of different biophysical and biochemical cues are growingly being developed. We demonstrate how the lamination of through-hole polymeric bio-functionalized membranes can be implemented to create complex bona fide micro-niches with differential 3D environmental properties using photoactive materials. Our approach enables to create micro-niches ranging in size from single cells to cell aggregates. They are bio-functionalized in 3D simultaneously with topographical featured, protein patterns and structured ECM surrogate with 1 micrometer resolution. We demonstrate how these niches extend in 3D the ability to pattern cells. We exemplify how they can be used to standardize cells shapes in 3D and to trigger the apico-basal polarization of single epithelial cells.

scholarly journals Adherent and suspension baby hamster kidney cells have a different cytoskeleton and surface receptor repertoire

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0246610
Author(s):  
Veronika Dill ◽  
Florian Pfaff ◽  
Aline Zimmer ◽  
Martin Beer ◽  
Michael Eschbaumer
Keyword(s):  
Cell Lines ◽  
Molecular Mechanisms ◽  
Animal Cell ◽  
Single Cells ◽  
Baby Hamster Kidney ◽  
Suspension Cells ◽  
Virus Growth ◽  
Bhk Cells ◽  
Cell Clones ◽  
Mouth Disease Virus

Animal cell culture, with single cells growing in suspension, ideally in a chemically defined environment, is a mainstay of biopharmaceutical production. The synthetic environment lacks exogenous growth factors and usually requires a time-consuming adaptation process to select cell clones that proliferate in suspension to high cell numbers. The molecular mechanisms that facilitate the adaptation and that take place inside the cell are largely unknown. Especially for cell lines that are used for virus antigen production such as baby hamster kidney (BHK) cells, the restriction of virus growth through the evolution of undesired cell characteristics is highly unwanted. The comparison between adherently growing BHK cells and suspension cells with different susceptibility to foot-and-mouth disease virus revealed differences in the expression of cellular receptors such as integrins and heparan sulfates, and in the organization of the actin cytoskeleton. Transcriptome analyses and growth kinetics demonstrated the diversity of BHK cell lines and confirmed the importance of well-characterized parental cell clones and mindful screening to make sure that essential cellular features do not get lost during adaptation.

scholarly journals An optogenetic tool to raise intracellular pH in single cells and drive localized membrane dynamics

2021 ◽  
Author(s):  
Caitlin E. T. Donahue ◽  
Michael D. Siroky ◽  
Katharine A. White
Keyword(s):  
Single Cell ◽  
Intracellular Ph ◽  
Single Cells ◽  
Cell Polarization ◽  
Membrane Dynamics ◽  
Cell Physiology ◽  
Single Cell Level ◽  
Cell Level ◽  
Cell Behaviors ◽  
Membrane Ruffling

AbstractIntracellular pH (pHi) dynamics are critical for regulating normal cell physiology. For example, transient increases in pHi (7.2-7.6) regulate cell behaviors like cell polarization, actin cytoskeleton remodeling, and cell migration. Most studies on pH-dependent cell behaviors have been performed at the population level and use non-specific methods to manipulate pHi. The lack of tools to specifically manipulate pHi at the single-cell level has hindered investigation of the role of pHi dynamics in driving single cell behaviors. In this work, we show that Archaerhodopsin (ArchT), a light-driven outward proton pump, can be used to elicit robust and physiological pHi increases over the minutes timescale. We show that activation of ArchT is repeatable, enabling the maintenance of high pHi in single cells for approximately 45 minutes. We apply this spatiotemporal pHi manipulation tool to determine whether increased pHi is a sufficient driver of membrane ruffling in single cells. Using the ArchT tool, we show that increased pHi in single cells can drive localized membrane ruffling responses within seconds and increased membrane dynamics (both protrusion and retraction events) compared to control cells. Overall, this tool allows us to directly investigate the relationship between increased pHi and cell behaviors such as membrane ruffling. This tool will be transformative in facilitating the experiments required to determine if increased pHi is a driver of these cell behaviors at the single-cell level.

scholarly journals Optogenetics reprogramming of planktonic cells for biofilm formation

2017 ◽  
Author(s):  
Aiguo Xia ◽  
Shuai Yang ◽  
Yajia Huang ◽  
Zhenyu Jin ◽  
Lei Ni ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Spatial Organization ◽  
Early Stage ◽  
Single Cells ◽  
Type Iv Pili ◽  
Guanosine Monophosphate ◽  
Planktonic Cells ◽  
Cell Behaviors ◽  
Type Iv ◽  
Illumination Method

AbstractSingle-cell behaviors play essential roles during early-stage biofilms formation. In this study, we evaluated whether biofilm formation could be guided by precisely manipulating single cells behaviors. Thus, we established an illumination method to precisely manipulate the type IV pili (TFP) mediated motility and microcolony formation of Pseudomonas aeruginosa by using a combination of a high-throughput bacterial tracking algorithm, optogenetic manipulation and adaptive microscopy. We termed this method as Adaptive Tracking Illumination (ATI). We reported that ATI enables the precise manipulation of TFP mediated motility and microcolony formation during biofilm formation by manipulating bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) levels in single cells. Moreover, we showed that the spatial organization of single cells in mature biofilms can be controlled using ATI. Thus, the established method (i.e., ATI) can markedly promote ongoing studies of biofilms.

scholarly journals Transfection of choanoflagellates illuminates their cell biology and the ancestry of animal septins

2018 ◽  
Vol 29 (25) ◽  
pp. 3026-3038 ◽  
Author(s):  
David S. Booth ◽  
Heather Szmidt-Middleton ◽  
Nicole King
Keyword(s):  
Cell Biology ◽  
Fluorescent Protein ◽  
Animal Cell ◽  
Single Cells ◽  
Dna Delivery ◽  
Cytoskeletal Proteins ◽  
Model Organisms ◽  
Protein Markers ◽  
Foreign Genes ◽  
Salpingoeca Rosetta

As the closest living relatives of animals, choanoflagellates offer unique insights into animal origins and core mechanisms underlying animal cell biology. However, unlike traditional model organisms, such as yeast, flies, and worms, choanoflagellates have been refractory to DNA delivery methods for expressing foreign genes. Here we report a robust method for expressing transgenes in the choanoflagellate Salpingoeca rosetta, overcoming barriers that have previously hampered DNA delivery and expression. To demonstrate how this method accelerates the study of S. rosetta cell biology, we engineered a panel of fluorescent protein markers that illuminate key features of choanoflagellate cells. We then investigated the localization of choanoflagellate septins, a family of GTP-binding cytoskeletal proteins that are hypothesized to regulate multicellular rosette development in S. rosetta. Fluorescently tagged septins localized to the basal poles of S. rosetta single cells and rosettes in a pattern resembling septin localization in animal epithelia. The establishment of transfection in S. rosetta and its application to the study of septins represent critical advances in the use of S. rosetta as an experimental model for investigating choanoflagellate cell biology, core mechanisms underlying animal cell biology, and the origin of animals.

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