scholarly journals Reverse and forward engineering of protein pattern formation

2018 ◽  
Vol 373 (1747) ◽  
pp. 20170104 ◽  
Author(s):  
Simon Kretschmer ◽  
Leon Harrington ◽  
Petra Schwille

Living systems employ protein pattern formation to regulate important life processes in space and time. Although pattern-forming protein networks have been identified in various prokaryotes and eukaryotes, their systematic experimental characterization is challenging owing to the complex environment of living cells. In turn, cell-free systems are ideally suited for this goal, as they offer defined molecular environments that can be precisely controlled and manipulated. Towards revealing the molecular basis of protein pattern formation, we outline two complementary approaches: the biochemical reverse engineering of reconstituted networks and the de novo design, or forward engineering, of artificial self-organizing systems. We first illustrate the reverse engineering approach by the example of the Escherichia coli Min system, a model system for protein self-organization based on the reversible and energy-dependent interaction of the ATPase MinD and its activating protein MinE with a lipid membrane. By reconstituting MinE mutants impaired in ATPase stimulation, we demonstrate how large-scale Min protein patterns are modulated by MinE activity and concentration. We then provide a perspective on the de novo design of self-organizing protein networks. Tightly integrated reverse and forward engineering approaches will be key to understanding and engineering the intriguing phenomenon of protein pattern formation. This article is part of the theme issue ‘Self-organization in cell biology’.

2012 ◽  
Vol 109 (38) ◽  
pp. 15283-15288 ◽  
Author(s):  
Jakob Schweizer ◽  
Martin Loose ◽  
Mike Bonny ◽  
Karsten Kruse ◽  
Ingolf Mönch ◽  
...  

In the living cell, proteins are able to organize space much larger than their dimensions. In return, changes of intracellular space can influence biochemical reactions, allowing cells to sense their size and shape. Despite the possibility to reconstitute protein self-organization with only a few purified components, we still lack knowledge of how geometrical boundaries affect spatiotemporal protein patterns. Following a minimal systems approach, we used purified proteins and photolithographically patterned membranes to study the influence of spatial confinement on the self-organization of the Min system, a spatial regulator of bacterial cytokinesis, in vitro. We found that the emerging protein pattern responds even to the lateral, two-dimensional geometry of the membrane such that, as in the three-dimensional cell, Min protein waves travel along the longest axis of the membrane patch. This shows that for spatial sensing the Min system does not need to be enclosed in a three-dimensional compartment. Using a computational model we quantitatively analyzed our experimental findings and identified persistent binding of MinE to the membrane as requirement for the Min system to sense geometry. Our results give insight into the interplay between geometrical confinement and biochemical patterns emerging from a nonlinear reaction–diffusion system.


Ingeniería ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 84
Author(s):  
David Anzola

Context: The concept of self-organization plays a major role in contemporary complexity science. Yet, the current framework for the study of self-organization is only able to capture some of the nuances of complex social self-organizing phenomena.Method: This article addresses some of the problematic elements in the study of social selforganization. For this purpose, it focuses on pattern formation, a feature of self-organizing phenomena that is common across definitions. The analysis is carried out through three main questions: where can we find these patterns, what are these patterns and how can we study these patterns.Results: The discussion shows that there is a high level of specificity in social self-organized phenomena that is not adequately addressed by the current complexity framework. It argues that some elements are neglected by this framework because they are relatively exclusive to social science; others, because of the relative novelty of social complexity.Conclusions: It is suggested that interdisciplinary collaboration between social scientists and complexity scientists and engineers is needed, in order to overcome traditional disciplinary limitations in the study of social self-organized phenomena.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1524 ◽  
Author(s):  
Manon C. Wigbers ◽  
Fridtjof Brauns ◽  
Ching Yee Leung ◽  
Erwin Frey

Important cellular processes, such as cell motility and cell division, are coordinated by cell polarity, which is determined by the non-uniform distribution of certain proteins. Such protein patterns form via an interplay of protein reactions and protein transport. Since Turing’s seminal work, the formation of protein patterns resulting from the interplay between reactions and diffusive transport has been widely studied. Over the last few years, increasing evidence shows that also advective transport, resulting from cytosolic and cortical flows, is present in many cells. However, it remains unclear how and whether these flows contribute to protein-pattern formation. To address this question, we use a minimal model that conserves the total protein mass to characterize the effects of cytosolic flow on pattern formation. Combining a linear stability analysis with numerical simulations, we find that membrane-bound protein patterns propagate against the direction of cytoplasmic flow with a speed that is maximal for intermediate flow speed. We show that the mechanism underlying this pattern propagation relies on a higher protein influx on the upstream side of the pattern compared to the downstream side. Furthermore, we find that cytosolic flow can change the membrane pattern qualitatively from a peak pattern to a mesa pattern. Finally, our study shows that a non-uniform flow profile can induce pattern formation by triggering a regional lateral instability.


2016 ◽  
Vol 113 (3) ◽  
pp. 548-553 ◽  
Author(s):  
Dominik Thalmeier ◽  
Jacob Halatek ◽  
Erwin Frey

Protein patterns are known to adapt to cell shape and serve as spatial templates that choreograph downstream processes like cell polarity or cell division. However, how can pattern-forming proteins sense and respond to the geometry of a cell, and what mechanistic principles underlie pattern formation? Current models invoke mechanisms based on dynamic instabilities arising from nonlinear interactions between proteins but neglect the influence of the spatial geometry itself. Here, we show that patterns can emerge as a direct result of adaptation to cell geometry, in the absence of dynamical instability. We present a generic reaction module that allows protein densities robustly to adapt to the symmetry of the spatial geometry. The key component is an NTPase protein that cycles between nucleotide-dependent membrane-bound and cytosolic states. For elongated cells, we find that the protein dynamics generically leads to a bipolar pattern, which vanishes as the geometry becomes spherically symmetrical. We show that such a reaction module facilitates universal adaptation to cell geometry by sensing the local ratio of membrane area to cytosolic volume. This sensing mechanism is controlled by the membrane affinities of the different states. We apply the theory to explain AtMinD bipolar patterns in Δ EcMinDE Escherichia coli. Due to its generic nature, the mechanism could also serve as a hitherto-unrecognized spatial template in many other bacterial systems. Moreover, the robustness of the mechanism enables self-organized optimization of protein patterns by evolutionary processes. Finally, the proposed module can be used to establish geometry-sensitive protein gradients in synthetic biological systems.


Author(s):  
Alexander Lukin ◽  
Oğuz Gülseren

Structural self-organizing and pattern formation are universal and key phenomena observed during growth and cluster-assembling of the carbyne-enriched nanostructured metamaterials at the ion-assisted pulse-plasma deposition. Fine tuning these universal phenomena opens access to designing the properties of the growing carbyne-enriched nano-matrix. The structure of bonds in the grown carbyne-enriched nano-matrices can be programmed by the processes of self-organization and auto-synchronization of nanostructures. We propose the innovative concept, connected with application of the universal Cymatics phenomena during the predictive growth of the carbyne-enriched nanostructured metamaterials. We also propose the self-organization approach for increase stability of the long linear carbon chains. The main idea of suggested concept is manipulating by the self-organized wave patterns excitation phenomenon and their distribution by the spatial structure and properties of the nanostructured metamaterial grows region through the new synergistic effect. Mentioned effect will be provided through the vibration-assisted self-organized wave patterns excitation along with simultaneous manipulating by their properties through the electric field. We propose to use acoustic activation of the plasma zone of nano-matrix growing. Interaction between the inhomogeneous electric field distribution generated on the vibrating layer and the plasma ions will serve as the additional energizing factor controlling the local pattern formation and self-organizing of the nano-structures. Suggested concept makes it possible to provide precise predictive designing the spatial structure and properties of the advanced carbyne-enriched nanostructured metamaterials.


2018 ◽  
Vol 373 (1747) ◽  
pp. 20170107 ◽  
Author(s):  
J. Halatek ◽  
F. Brauns ◽  
E. Frey

Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article, we review quantitative models for intracellular Min protein patterns in Escherichia coli , Cdc42 polarization in Saccharomyces cerevisiae and the bipolar PAR protein patterns found in Caenorhabditis elegans . By analysing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as ‘activators’, ‘inhibitors’ or ‘substrate depletion’. Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction–diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics. This article is part of the theme issue ‘Self-organization in cell biology’.


Author(s):  
Dieter Buyst ◽  
V. Gheerardijn ◽  
J. Van Den Begin ◽  
A. Madder ◽  
J. C. Martins

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