PERspECTIVES steady-state spatial patterns could also arise TIMELINE from such processes in living systems21. The full formalization of the nature of Self-organization in cell biology: self-organization processes came from the work of Prigogine on instabilities and the a brief history emergence of organization in ‘dissipative systems’ in the 1960s22–24, and from Haken who worked on similar issues under the Eric Karsenti name of synergetics11 (TIMELINE). Abstract | Over the past two decades, molecular and cell biologists have made It was clear from the outset that the emergence of dynamical organization important progress in characterizing the components and compartments of the observed in physical and chemical systems cell. New visualization methods have also revealed cellular dynamics. This has should be of importance to biology, and raised complex issues about the organization principles that underlie the scientists who are interested in the periodic emergence of coherent dynamical cell shapes and functions. Self-organization manifestations of life and developmental concepts that were first developed in chemistry and physics and then applied to biology have been actively working in this field19,25–29. From a more general point various morphogenetic problems in biology over the past century are now of view, Kauffman built on the ideas of beginning to be applied to the organization of the living cell. Prigogine and Haken in an attempt to explain the origin of order in biology30–32. One of the most fundamental problems in this complex state of living matter as a self- Self-organization was also invoked to biology concerns the origin of forms and organized end8–10. This led him to question explain the formation of regular patterns in their associated functions. This has been a the validity of using the causality principle the fur of animals and the collective behav- long-lasting question in developmental of classical physics to explain life, and to iour of organisms in ant colonies, termite biology, but similar questions must also suggest that a new kind of science would be nest building, schools of fish and flocks of be addressed at the cellular level. Since required to study how purpose and means birds33,34. The importance of self-organiza- the discovery of the structure of DNA, the are intricately connected8. tion processes in molecular cell biology genome has often been thought of as the The new science he was talking about began to be recognized in the 1980s and overriding architect: a given combination did emerge much later, from observations 1990s1,35–40, but only really started to gain of genes that determines the phenotype and studies made by chemists and physicists momentum recently6,41–43 (TIMELINE). through a linear chain of causal events. who discovered new, more complex forms In the following article, I do not deal The problem is that embryogenesis and of causality than what Kant had foreseen11,12. with developmental biology issues but dynamic cell forms and functions emerge Ironically, although Kant attempted to specifically focus on how self-organization from multiple molecular interactions and characterize life as a self-organization principles and mechanisms (BOX 1) can help interconnected regulatory feedback loops1–4. process in opposition to non-living mat- to understand subcellular and whole-cell Moreover, many parameters, such as physi- ter, the first well-defined concepts and morphogenesis. I first summarize the cal constraints and collective behaviours, are observations of self-organized processes essence of the theory of self-organization in not under the direct control of the genome. came from theoretical considerations by physico-chemical systems in simple terms. Therefore, we cannot hope to explain cell Lotka13,14, from chemistry by Bray15 and I then show how this concretely applies to morphogenesis, for example, by invoking from the Belousov–Zhabotinsky reaction16–19 some examples of cell organization and simple linear chains of causal events that link (TIMELINE). Chemical oscillations emerged function. genes to phenotypes5–7. from reaction–diffusion processes that It seems that the philosopher Kant was were formalized in mathematical terms Self-organization concepts the first to define life as a “self-organized, by Kolmogorov et al.20 in the 1930s and by The initial definition of self-organization self-reproducing” process (TIMELINE). Turing in the 1950s, who predicted that by Kant as a characteristic of living systems Through pure reasoning, he defined life as implied the existence of a loop between the emergence of functions by self-organiza- organization and function. A simpler tion. He said that in an organism, every It was clear from the outset definition used by modern scientists is that part owes its existence and origin to that that the emergence of dynamical dynamic organization emerges from the of the other parts, with the functions organization observed in physical collective behaviour of ‘agents’, the individual that are attributed to a complete living organ properties of which cannot account for or organism emerging from the properties and chemical systems should be the properties of the final dynamic pattern. of the parts and of the whole. He defined of importance to biology... This definition is more general and has the natURE REVIEWS | MOLECULAR CELL BIOLOGY VolUME 9 | MARch 2008 | 255 © 2008 Nature Publishing Group PERS P ECTIVES Timeline | Key events in the application of self-organization concepts in cell biology (1972–1977) Biological pattern formation30,31. (1999–2005) Kant and the self- First oscillating Exploratory Reaction–diffusion organized nature chemical reaction Turing (1972–1977) Oscillations behaviours in cell Self-organized and intracellular (2005–2007) The self- of life8–10. in solution15. patterns21. in glycolysis25–27. morphogenesis36. microtubule patterns37,38. morphogenesis3,4. organized cell41,43,80,88,89. 1790 1900 1921 1951 1952 1967 1972 1977 1986 1990 1991 1997 1999 2003 2005 Discovery of the Belousov–Zhabotinsky Dissipative systems11,22. (1977–1984) Experimental Turing (1997–2001) Emergent Self-organized cell polarity91–94. Bénard rolls44. oscillatory reaction16–19. Multicellular29,33 patterns46,47. cytoskeleton patterns and mitotic spindle from collective self-organization39. Self-organized animal behaviours57,58. populations33,34. advantage of being applicable to systems that Origins in thermodynamics. At first sight, energy that flows through it can be used to do not necessarily acquire a function, even the spontaneous emergence of order in the decrease its entropy (that is, generate order). though they become dynamically organ- universe contradicts the second law of thermo- Molecules can suddenly organize themselves ized. The understanding of the emergence dynamics: a thermodynamically closed sys- in dynamic patterns. Bénard rolls44,45 (long- of function can be studied separately. The tem settles in the most disordered state (that itudinal cylinders of liquid molecules that other advantage of this definition is that it is, the state with the highest entropy, when form precise and stable dynamic patterns) establishes how self-organized dynamical molecules occupy all of the space randomly; represent such an example and were called systems should be studied: the goal of the FIG. 1a). Ordered states can and do emerge at ‘dissipative structures’ by Prigogine22 (FIG. 1b). science of self-organization is to identify thermodynamic equilibrium (for example, the principles and mechanisms by which an crystals, lipid bilayers, molecular complex Collective behaviour and the Bénard rolls. ensemble of agents in interaction evolves formation), but they are static. Bénard rolls form when a liquid is heated towards a particular dynamical temporal or In a thermodynamically open system from below, which generates a temperature spatial pattern. that receives energy from the outside, the gradient. Molecules at the bottom of the container are more agitated than at the top, creating a lighter layer of liquid than that Box 1 | Self-organization concepts and mechanisms at the top. Roll formation results from local Self-organization occurs when elements interact dynamically with each other to generate a system instabilities that lead the system to break its that acquires emergent properties that cannot be directly predicted from the individual properties symmetry when molecules start to behave of the elements. This only happens when the system dissipates energy. collectively. This happens at different critical temperatures for different fluids, but always Principles Mechanisms Examples in the cell occurs when all of the parameters balance Thermodynamics: non- Thermal, chemical or other ATP consumption coupled to each other so that they satisfy a universal equilibrium thermodynamics. energy dissipation that is dynamic pattern formation. number, called the Rayleigh number, which associated with dynamic 33 pattern formation. equals 1708 under specific conditions . The system can generate rolls that, at Symmetry breaking: occurs Gravity, temperature or Intrinsic asymmetry of a given position in the container, move when a system switches chemical gradients, local agents, nonlinear reactions, from one symmetry level to fluctuations. stereospecific localization clockwise or counter-clockwise with alternate another. of enzymes, pre-existing orientation. When the temperature is raised structures. to the critical value, the system bifurcates Emergence: a new property Collective effects