Self-organization in biological systems

Biological systems are considered that are capable of dynamic self-organization, i.e., spontaneous emergence of spatio-temporal order with the formation of various spatio-temporal patterns. A cell is involved in the organization of ontogenesis of all stages. Embryonic cells exhibit coordinated social behavior and generate ordered morphological patterns displaying variability and equifinality of development. Physical and topological patterns are essential for biological systems as an imperative that restricts and directs biological morphogenesis. Biological self-organization is directed and fixed by natural selection during which selection of the most sustainable, flexible, modular systems capable of adaptive self-organization occurs.     

Symmetry and entropy of biological patterns: discrete Walsh functions for 2D image analysis

To quantify symmetry and entropy inherent in the discrete patterns such as spatial self-organization in cell sorting and mussel bed ecosystems, we introduce the discrete Walsh analysis. This analysis enables us to estimate the degree of the complicated symmetry, and to extract the symmetry from the pattern that seems to be asymmetric. The results obtained in this paper are summarized as follows. (I) The geometrical patterns of the cell sorting become systematic with the predominance of the particular symmetry. This implies that not only the entropy but also the particular symmetry can decrease in the biological process. (II) The magnitude of the symmetry is related to the absolute value of the adhesion, and the type of the symmetry is related to the sign of the adhesion. That is, centro-symmetry dominates in the cell sorting pattern caused by large negative adhesion, and double symmetry dominates in the pattern caused by large positive adhesion. (III) Spatial self-organization in mussel bed is accompanied by the decreasing of the centro-symmetry. This implies that the positive "adhesion" between mussel individuals increases with time. (IV) In the biological process, the Curie symmetry breaking occurs at intervals.     

Chirality as a primary switch of hierarchical levels in molecular biological systems

A synergetic law, being of common physicochemical and biological sense, is formulated: any evolving system that possesses an excess of free energy and elements with chiral asymmetry, while being within one hierarchical level, is able to change the type of symmetry in the process of self-organization increasing its complexity but preserving the sign of prevailing chirality (left — L or right — D twist). The same system tends to form spontaneously a sequence of hierarchical levels with alternating chirality signs of de novo formed structures and with an increase of the structures’ relative scales. In living systems, the hierarchy of conjugated levels of macromolecular structures that begins from the “lowest” asymmetric carbon serves as an anti-entropic factor as well as the structural basis of “selected mechanical degrees of freedom” in molecular machines. During transition of DNA to a higher level of structural and functional organization, regular alterations of the chirality sign D-L-D-L and L-D-L-D for DNA and protein structures, respectively, are observed. Sign-alternating chiral hierarchies of DNA and protein structure, in turn, form a complementary conjugated chiral pair that represents an achiral invariant that “consummates” the molecular-biological block of living systems. The ability of a carbon atom to form chiral compounds is an important factor that determined the carbon basis of living systems on the Earth as well as their development though a series of chiral bifurcations. The hierarchy of macromolecular structures demarcated by the chirality sign predetermined the possibility of the “block” character of biological evolution.     

Cells in the system of multicelular organism from positions of non-linear dynamics

The organism physiological systems forming a hierarchic network with mutual dependence and subordination can be considered as systems with non-linear dynamics including positive and negative feedbacks. In the course of evolution there occurred selection of robust, flexible, modular systems capable for adaptive self-organization by non-linear interaction of components, which leads to formation of the ordered in space and time robust and plastic organization of the whole. Cells of multicellular organisms are capable for coordinated “social” behavior with formation of ordered cell assemblies, which provides a possibility of morphological and functional variability correlating with manifestations of the large spectrum of adaptive reactions. The multicellular organism is the multilevel system with hierarchy of numerous subsystems capable for adaptive self-organization; disturbance of their homeostasis can lead to pathological changes. The healthy organism regulates homeostasis, self-renewal, differentiation, and apoptosis of cells serving its parts and construction blocks by preserving its integrity and controlling behavior of cells. The systemic approach taking into account biological regularities of the appearance and development of functions in evolution of multicellular organisms opens new possibilities for diagnostics and treatment of many diseases.     

Historical and conceptual background of self-organization by reactive processes

Order, form, pattern and organization are properties central to much living matter. The physicochemical processes by which an initially homogeneous solution of reacting chemicals or biochemicals might self-organize is hence a question of fundamental biological importance. In most cases, solutions of reacting chemicals in a test-tube do not self-organize. Because of this, for many years, it was not thought possible that reactive processes could result in self-organization. However, progressively over the last hundred years, it has been shown that this is not always the case, and under certain conditions, the combination of reaction with molecular diffusion can lead to macroscopic self-organization. In 'complex' systems comprised of populations of strongly coupled elements, new 'emergent' properties, such as self-organization, arise by way of the dynamics of the system. Self-organizing reaction-diffusion systems form a specific type of complex system. Here, I will give a personal overview of the conceptual and historical background to this approach with an emphasis on biological self-organization.     

Self-Organization in Living Cells: Networks of Protein Machines and Nonequilibrium Soft Matter

Microscopic self-organization phenomena inside a living cell should not represent merely a reduced copy of self-organization in macroscopic systems. A cell is populated by active protein machines that communicate via small molecules diffusing through the cytoplasm. Mutual synchronization of machine cycles can spontaneously develop in such networks – an effect which is similar to coherent laser generation. On the other hand, an interplay between reactions, diffusion and phase transitions in biological soft matter may lead to the formation of stationary or traveling nonequilibrium nanoscale structures.     

Relationship between three-dimensional arrays of "lipidic particles" and bicontinuous cubic lipid phases

Several lipid-water mixtures form phases that give rise to freeze-fracture replicas exhibiting three-dimensional regular arrays of closely packed globular elements, often called "lipidic particles". These phases have often been poorly classified with respect to long-range organization and symmetry and have in most cases been asserted to be built up by closed lipid aggregates, such as reversed micelles. However, studies of phases giving rise to the above-mentioned freeze-fracture replicas, with X-ray diffraction and the nuclear magnetic resonance pulsed field gradient diffusion technique, have revealed that they are cubic liquid-crystalline phases and with one exception bicontinuous phases, i.e., cubic phases in which both the hydrocarbon and the water regions are continuous. Up to now the only known exception is a cubic phase composed of closed rod-shaped micelles of the normal type. Thus it is not possible to decide from a freeze-fracture image of a cubic phase, showing three-dimensional arrays of "lipidic particles", if the phase is bicontinuous or composed of closed lipid aggregates. Hitherto, it has not been shown that a biological membrane lipid-water system is able to form a cubic liquid-crystalline phase consisting of reversed micelles. The existence of such a phase is also improbable considering the location in the phase diagrams of cubic phases formed by biological membrane lipid-water systems.     

Organisational closure in biological organisms

The central aim of this paper consists in arguing that biological organisms realize a specific kind of causal regime that we call "organisational closure"; i.e., a distinct level of causation, operating in addition to physical laws, generated by the action of material structures acting as constraints. We argue that organisational closure constitutes a fundamental property of biological systems since even its minimal instances are likely to possess at least some of the typical features of biological organisation as exhibited by more complex organisms. Yet, while being a necessary condition for biological organization, organisational closure underdetermines, as such, the whole set of requirements that a system has to satisfy in order to be taken as a paradigmatic example of organism. As we suggest, additional properties, as modular templates and control mechanisms via dynamical decoupling between constraints, are required to get the complexity typical of full-fledged biological organisms.     

Cellular signaling: aspects for tumor diagnosis and therapy.

Cells are organic microsystems with functional compartments interconnected by complex signal chains. Intracellular signaling routes and signal reception from the extracellular environment are characterized by redundancy, i.e., parallel pathways exist. If a cell is exposed to an external "signal input", the signal processing elements within the cell provide a response that will be a pattern of reactions manifest as a metabolic, morphologic or electric "signal output". Cell-chip hybrid structures are miniaturized analytical systems with the capability to monitor such cell responses in real time and under continuous control of the environmental conditions. A system analysis approach gives an idea of how the biological component of these hybrid structures works. This is exemplified by the putative role of the microenvironmental pH as a parameter of the utmost importance for the malignant "mode" of tumor cells, which can be monitored and modeled on such hybrid structures.     

Means, Advantages and Limits of Merging Biology with Technology

The natural world spent billions of years in solution-finding during evolution, which could benefit Technology. How do we put that in a nutshell? Biological systems are more complex than the most complex current technology. Any given functiofi and effect are simultaneously coordinated and linked with others at many levels of biological organisation-from cell organelle to organism, to population and ecosystem. Technology does not have tools to deal with the complexity and “goalintendedness“ of living systems. But limits for interaction exist on both sides-Biological science itself is also too empirical and not mature enough to provide a solid base for correlating living with technical systems. Moving towards a synthesis, where engineers can utilize the vast amount of available biological data, we suggest using a tool called “Theory of Inventive Problem Solving“ (TRIZ) and clarifying some important methodological issues, which have not previously been recognised in bionic engineering: 1) Requirement for more appropriate definitions of “system“, “effect“, “function“, “law“ and “rule“. 2) Requirement for understanding or even measuring the degree of contradiction or analogy between functions in biological and artificial and/or non-living engineering system-there is no simple direct correlation between what engineers find useful and what biology does.     

2.8 A crystal structures of recombinant fibrinogen fragment D with and without two peptide ligands: GHRP binding to the "b" site disrupts its nearby calcium-binding site

We report two crystal structures, each at a resolution of 2.8 A, of recombinant human fibrinogen fragment D (rfD) in the absence and presence of peptide ligands. The bound ligands, Gly-Pro-Arg-Pro-amide and Gly-His-Arg-Pro-amide, mimic the interactions of the thrombin exposed polymerization sites, "A" and "B", respectively. This report is the first to describe the structure of fragment D in the presence of both peptide ligands. The structures reveal that recombinant fibrinogen is nearly identical to the plasma protein but with minor changes, like the addition of a proximal fucose to the carbohydrate linked to residue betaGln364, and slightly different relative positions of the beta- and gamma-modules. Of major interest in our structures is that a previously identified calcium site in plasma fibrinogen is absent when Gly-His-Arg-Pro-amide is bound. The peptide-dependent loss of this calcium site may have significant biological implications that are further discussed. These structures provide a foundation for the detailed structural analysis of variant recombinant fibrinogens that were used to identify critical functional residues within fragment D.     

Scale invariance of biosystems: From embryo to community

Phenomena having the property of a scale invariance (that is, maintaining invariable structure in certain range of scales) are typical for biosystems of different levels. In this review, main manifestations of the scale-invariant phenomena at different levels of biological organization (including ontogenetic aspects) are stated, and the reasons of such wide distribution of fractal structures in biology are discussed. Almost all biological systems can be described in terms of synergetics as open nonequilibrium systems that exist due to substance and energy flow passing through them. The phenomenon of self-organization is typical for such dissipative systems; maintenance of energy flow requires the existence of complex structures that emerge spontaneously in the presence of the appropriate gradient. Critical systems, which form as a results of their activity scale-invariant structures (that are a kind of distribution channels), are optimal relative to the efficiency of substance and energy distribution. Thus, scale invariance of biological phenomena is a natural consequence of their dissipative nature.     

Phase diagram of deep rough mutant lipopolysaccharide from Salmonella minnesota R595.

The structural polymorphism of deep rough mutant lipopolysaccharide--in many biological systems the most active endotoxin--from Salmonella minnesota strain R595 was investigated as function of temperature, water content, and Mg2+ concentration. Differential scanning calorimetry was used to determine the amount of bound water and the enthalpy change at the beta<==>alpha gel to liquid crystalline acyl chain melting. The onset, midtemperature Tc, and completion of the beta<==>alpha phase transition were studied with Fourier-transform infrared spectroscopy. Synchrotron radiation X-ray diffraction was used to characterize the supramolecular three-dimensional structures in each phase state. The results indicate an extremely complex dependence of the structural behavior of LPS on ambient conditions. The beta<==>alpha acyl chain melting temperature Tc lying at 30 degrees C at high water content (95%) increases with decreasing water content reaching a value of 50 degrees C at 30% water content. Concomitantly, a broadening of the transition range takes place. At still lower water content, no distinct phase transition can be observed. This behavior is even more clearly expressed in the presence of Mg2+. In the lower water concentration range (< 50%) at temperatures below 70 degrees C, only lamellar structures can be observed independent of the Mg2+ concentration. This correlates with the absence of free water. Above 50% water concentration, the supramolecular structure below 70 degrees C strongly depends on the [LPS]:[Mg2+] ratio. For large [LPS]:[Mg2+] ratios, the predominant structure is nonlamellar, for smaller [LPS]:[Mg2+] ratios there is a superposition of lamellar and nonlamellar structures. At an equimolar ratio of LPS and Mg2+ a multibilayered organization is observed. The nonlamellar structures can be assigned in various cases to structures with cubic symmetry with periodicities between 12 and 16 nm. Under all investigated conditions, a transition into the hexagonal II structure takes place between 70 and 80 degrees C. These observations are discussed in relation to the biological importance of LPS as constituent of the outer membrane of gram-negative bacteria and as potent inducer of biological effects in mammals.     

Modular optical topometric sensor for 3D acquisition of human body surfaces and long-term monitoring of variations.

Optical topometric 3D sensors such as laser scanners and fringe projection systems allow detailed digital acquisition of human body surfaces. For many medical applications, however, not only the current shape is important, but also its changes, e.g., in the course of surgical treatment. In such cases, time delays of several months between subsequent measurements frequently occur. A modular 3D coordinate measuring system based on the fringe projection technique is presented that allows 3D coordinate acquisition including calibrated color information, as well as the detection and visualization of deviations between subsequent measurements. In addition, parameters describing the symmetry of body structures are determined. The quantitative results of the analysis may be used as a basis for objective documentation of surgical therapy. The system is designed in a modular way, and thus, depending on the object of investigation, two or three cameras with different capabilities in terms of resolution and color reproduction can be utilized to optimize the set-up.     

A self-organizing neural network sharing features of the mammalian visual system

This paper describes a neural network model whose structure is designed to closely fit neuroanatomical and-physiological data, and not to be most suitable for rigorous mathematical analysis.It is shown by computer simulation that a process of self-organization that departs from a fixed retinotopic order at peripheral layers and includes hebbian modifications of synaptic connectivity at higher processing levels leads to a system that is capable of mimicking various functions of visual systems:In the initial state the overall structure of the network is preset, individual connections at higher levels are randomly selected and their strength is initialized with random numbers.For this model the outcome of the self-organization process is determined by the stimulation during the developmental phase. Depending on the type of stimuli used the model can either develop towards a featureselective preprocessor stage in a complex vision system or towards a subsystem for associative recall of abstract patterns.This flexibility supports the hypothesis that the principles embodied are rather universal and can account for the development of various nervous system structures.Presented at teh 9th Cybernetics-Congress, Göttingen, March 1986     

Automated culture of aquatic model organisms: shrimp larvae husbandry for the needs of research and aquaculture

Modern research makes frequent use of animal models, that is, organisms raised and bred experimentally in order to help the understanding of biological and chemical processes affecting organisms or whole environments. The development of flexible, reprogrammable and modular systems that may help the automatic production of ‘not-easy-to-keep’ species is important for scientific purposes and for such aquaculture needs as the production of alive foods, the culture of small larvae and the test of new culture procedures. For this reason, we planned and built a programmable experimental system adaptable to the culture of various aquatic organisms, at different developmental stages. The system is based on culture cylinders contained into operational tanks connected to water conditioning tanks. A programmable central processor unit controls the operations, that is, water changes, temperature, light irradiance, the opening and closure of valves for the discharge of unused foods, water circulation and filtration and disinfection systems, according to the information received by various probes. Various devices may be set to modify water circulation and water changes to fulfil the needs of given organisms, to avoid damage of delicate structures, improve feeding performances and reduce the risk of movements over the water surface. The results obtained indicate that the system is effective in the production of shrimp larvae, being able to produce Hippolyte inermis post-larvae with low mortality as compared with the standard operation procedures followed by human operators. Therefore, the patented prototype described in the present study is a possible solution to automate and simplify the rearing of small invertebrates in the laboratory and in production plants.     

The principles of collective animal behaviour

In recent years, the concept of self-organization has been used to understand collective behaviour of animals. The central tenet of self-organization is that simple repeated interactions between individuals can produce complex adaptive patterns at the level of the group. Inspiration comes from patterns seen in physical systems, such as spiralling chemical waves, which arise without complexity at the level of the individual units of which the system is composed. The suggestion is that biological structures such as termite mounds, ant trail networks and even human crowds can be explained in terms of repeated interactions between the animals and their environment, without invoking individual complexity. Here, I review cases in which the self-organization approach has been successful in explaining collective behaviour of animal groups and societies. Ant pheromone trail networks, aggregation of cockroaches, the applause of opera audiences and the migration of fish schools have all been accurately described in terms of individuals following simple sets of rules. Unlike the simple units composing physical systems, however, animals are themselves complex entities, and other examples of collective behaviour, such as honey bee foraging with its myriad of dance signals and behavioural cues, cannot be fully understood in terms of simple individuals alone. I argue that the key to understanding collective behaviour lies in identifying the principles of the behavioural algorithms followed by individual animals and of how information flows between the animals. These principles, such as positive feedback, response thresholds and individual integrity, are repeatedly observed in very different animal societies. The future of collective behaviour research lies in classifying these principles, establishing the properties they produce at a group level and asking why they have evolved in so many different and distinct natural systems. Ultimately, this research could inform not only our understanding of animal societies, but also the principles by which we organize our own society.     

Intermodular communication in polyketide synthases: comparing the role of protein-protein interactions to those in other multidomain proteins

Although the role of protein-protein interactions in transducing signals within biological systems has been extensively explored, their relevance to the channeling of intermediates in metabolism is not widely appreciated. Polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) are two related families of modular megasynthases that channel covalently bound intermediates from one active site to the next. Recent biochemical studies have highlighted the importance of protein-protein interactions in these chain transfer processes. The information available on this subject is reviewed, and its possible mechanistic implications are placed in context by comparisons with selected well-studied multicomponent protein systems.     

On the definition, nomenclature and classification of water channel proteins (aquaporins and relatives)

A water channel protein (WCP) or a water channel can be defined as a transmembrane protein that has a specific three-dimensional structure with a pore that provides a pathway for water permeation across biological membranes. The pore is formed by two highly conserved regions in the amino acid sequence, called NPA boxes (or motifs) with three amino acid residues (asparagine-proline-alanine, NPA) and several surrounding amino acids. The NPA boxes have been called the "signature" sequence of WCPs. WCPs are a family of proteins belonging to the Membrane Intrinsic Proteins (MIPs) superfamily. In addition, in the MIP superfamily (with more than 1000 members) there are also proteins with no channel activity. The WCP family include three subfamilies: aquaporins, aquaglyceroporins and S-aquaporins. (1) The aquaporins (AQPs) are water selective or specific water channels, also named by various authors as "orthodox", "ordinary", "conventional", "classical", "pure", "normal", or "sensu strictu" aquaporins); (2) The aquaglyceroporins are permeable to water, but also to other small uncharged molecules, in particular glycerol; this family includes the glycerol facilitators, abbreviated as GlpFs, from glycerol permease facilitators. The "signature" sequence for aquaglyceroporins is the aspartic acid residue (D) in the second NPA box. (3) The third subfamily of WCPs have little conserved amino acid sequences around the NPA boxes, unclassifiable to the first two subfamilies. I recommend to use always for this subfamily the name S-aquaporins. They are also named "superaquaporins", "aquaporins with unusual (or deviated) NPA boxes", "subcellular aquaporins", or "sip-like aquaporins". I also recommend to use always the spelling aquaporin (not aquaporine), and, for various AQPs, the abbreviation AQP followed immediately by the number, (e.g. AQP1), with no space or - which might create confusions with "minus".