The view is presented that extracellular architecture in plant cell walls results from an interplay between molecular self‐assembly and mechanical reorientation due to growth forces. A key initial self‐assembly step may involve hemicelluloses. It is suggested that hemicelluloses may self‐assemble into a helicoid via a cholesteric liquid crystalline phase; the detailed molecular structure of hemicelluloses (stiff backbone, bulky side chains, and the presence of asymmetric carbon atoms) is shown to be consistent with cholesteric requirements for such (...) self‐assembly. Since hemicelluloses are hydrogen‐bonded to the periphery of cellulose microfibrils, the cellulose could then itself become helicoidally arranged. Such ‘universal plywood’ structure is found in the walls of a wide variety of plants, and in several types of cell (including wood). The permanent effects of growth stresses on patterns seen in sections of helicoids are displayed by computer graphics plots, and the expected changes in stiffness are calculated. (shrink)

Basement membranes are thin sheets of extracellular proteins situated in close contact with cells at various locations in the body. They have a great influence on tissue compartmentalization and cellular phenotypes from early embryonic development onwards. The major constituents of all basement membranes are collagen IV and laminin, which both exist as multiple isoforms and each form a huge irregular network by self assembly. These networks are connected by nidogen, which also binds to several other components (proteoglycans, fibulins). Basement membranes (...) are connected to cells by several receptors of the integrin family, which bind preferentially to laminins and collagen IV, and via some lectin‐type interactions. The formation of basement membranes requires cooperation between different cell types since nidogen, for example, is usually synthesized by cells other than those exposed to the basement membranes. Thus many molecular interactions, of variable affinities, determine the final shape of basement membranes and their preferred subanatomical localization. (shrink)

Lately there has been a growing interest in evolutionary studies concerning how the regularities and patterns found in the living cell could have emerged spontaneously by way of self-assembly and self-organization. It is reasonable to postulate that the chemical compounds found in the primitive Earth would have mostly been very simple in nature, and would have been immersed in the natural dynamics of the physical world, some of which would have involved self-organization. It seems likely that some molecular processes (...) self-organized spontaneously into a hierarchy of complex behaviours. Our conceptual search herein reaches back to the time when prebiotic phenomena began to take shape. This was before the origin of life, so in this paper we hope to shed new light on some of the theoretical issues that surround the ways in which cellular organization might have evolved without the aid of replicated information. (shrink)

An astonishingly diverse biomolecular circuitry orchestrates the functioning machinery underlying every living cell. These biomolecules and their circuits have been engineered not only for various industrial applications but also to perform other atypical functions that they were not evolved for—including computation. Various kinds of computational challenges, such as solving NP‐complete problems with many variables, logical computation, neural network operations, and cryptography, have all been attempted through this unconventional computing paradigm. In this review, we highlight key experiments across three different ‘‘eras’’ (...) of molecular computation, beginning with molecular solutions, transitioning to logic circuits and ultimately, more complex molecular networks. We also discuss a variety of applications of molecular computation, from solving NP‐hard problems to self‐assembled nanostructures for delivering molecules, and provide a glimpse into the exciting potential that molecular computing holds for the future. Also see the video abstract here: https://youtu.be/9Mw0K0vCSQw. (shrink)

The Nanoessence project aims to examine life at a sub-cellular level, re-examining space and scale within the human context. A single HaCat skin cell is analysed with an Atomic Force Microscope (AFM) to explore comparisons between, life and death at a nano level. The humanistic discourse concerning life is now being challenged by nanotechnological research that brings into question the concepts of what constitutes living. The Nanoessence project research is based on data gathered as part of a residency at SymbioticA, (...) Centre of Excellence in Biological Arts, University of Western Australia and the Nanochemistry Research Institute, (NRI) Curtin University of Technology. The space of the body can be seen at an atomic level as having no defining boundaries. More generally, molecular self-assembly seeks to use concepts of supramolecular chemistry, and molecular recognition in particular, to cause single-molecule components to automatically arrange themselves into some useful conformation (reference Wikipedia). Nano assembly, or bottom-up approach, is the construction of a supramolecular chemistry by the assembly of nanoscopic particles, or even atoms and molecules. The proposal for nanotechnology to reshape nature atom by atom develops an interesting debate as to the constitution of life. The Nanoessence project aims to construct a physical experience to examine this scientific and metaphysical world. Nanoessence is an interactive audio-visual installation. In the Nanoessence installation the viewer will interface with the visual and sonic presentation through his or her own breath. In the context of the project breath has a strong conceptual and metaphorical link to a Biblical inception of life. The project attempts to maintain a high quality of authentic data to engage the viewer in a sensorial qualitative experience of quantitative data. (shrink)

In this thesis, I discuss the organism's self-organization from the perspective of relational ontology. I critically examine scientific and philosophical sources that appeal to the concept of self-organization. By doing this, I aim to carry out a thorough investigation into the underlying reasons of emergent order within the ontogeny of the organism. Moreover, I focus on the relation between universal dynamics of organization and the organization of living systems. I provide a historical review of the development of modern ideas related (...) to self-organization. These ideas have been developed in relation to various research areas including thermodynamics, molecular biology, developmental biology, systems theory, and so on. In order to develop a systematic understanding of the concept, I propose a conceptual distinction between transitional self-organization and regulative self-organization. The former refers to the spontaneous emergence of order, whereas the latter refers to the self-maintaining characteristic of the living systems. I show the relation between these two types of organization within biological processes. I offer a critical analysis of various theories within the organizational approach. Several ideas and notions in these theories originate from the early studies in cybernetics. More recently, autopoiesis and the theory of biological autonomy asserted certain claims that were critical toward the ideas related to self-organization. I advocate a general theory of self-organization against these criticisms. I also examine the hierarchical nature of the organism's organization, as this is essential to understand regulative self-organization. I consider the reciprocal relation between bottom-up and top-down dynamics of organization as the basis of the organism's individuation. To prove this idea, I appeal to biological research on molecular self-assembly, pattern formation (including reaction-diffusion systems), and the self-organized characteristic of the immune system. Finally, I promote the idea of diachronic emergence by drawing support from biological self-organization. I discuss the ideas related to constraints, potentiality, and dynamic form in an attempt to reveal the emergent nature of the organism. To demonstrate the dynamicity of form, I examine research into biological oscillators. I draw the following conclusions: synchronic condition of the organism is irreducibly processual and relational, and this is the basis of the organism's potentiality for various organizational states. (shrink)

A simple molecular system is described consisting of the reciprocal linkage between an autocatalytic cycle and a self-assembling encapsulation process where the molecular constituents for the capsule are products of the autocatalysis. In a molecular environment sufficiently rich in the substrates, capsule growth will also occur with high predictability. Growth to closure will be most probable in the vicinity of the most prolific autocatalysis and will thus tend to spontaneously enclose supportive catalysts within the capsule interior. If (...) subsequently disrupted in the presence of new substrates, the released components will initiate production of additional catalytic and capsule components that will spontaneously re-assemble into one or more autocell replicas, thereby reconstituting and sometimes reproducing the original. In a diverse molecular environment, cycles of disruption and enclosure will cause auto-cells to incidentally encapsulate other molecules as well as reactive substrates. To the extent that any captured molecule can be incorporated into the autocatalytic process by virtue of structural degeneracy of the catalytic binding sites, the altered autocell will incorporate the new type of component into subsequent replications. Such altered autocells will be progenitors of “lineages” with variant characteristics that will differentially propagate with respect to the availability of commonly required substrates. Autocells are susceptible to a limited form of evolution, capable of leading to more efficient, more environmentally fitted, and more complex forms. This provides a simple demonstration of the plausibility of open-ended reproduction and evolvability without self-replicating template molecules or maintenance of persistent nonequilibrium chemistry. This model identifies an intermediate domain between prebiotic and biotic systems and bridges the gap from nonequilibrium thermodynamics to life. (shrink)

We consider how an epistemic network might self-assemble from the ritualization of the individual decisions of simple heterogeneous agents. In such evolved social networks, inquirers may be significantly more successful than they could be investigating nature on their own. The evolved network may also dramatically lower the epistemic risk faced by even the most talented inquirers. We consider networks that self-assemble in the context of both perfect and imperfect communication and compare the behaviour of inquirers in each. This provides a (...) step in bringing together two new and developing research programs, the theory of self-assembling games and the theory of network epistemology. (shrink)

This article considers how a generalized signalling game may self-assemble as the saliences of the agents evolve by reinforcement on those sources of information that in fact lead to successful action. On the present account, generalized signalling games self-assemble even as the agents co-evolve meaningful representations and successful dispositions for using those representations. We will see how reinforcement on successful information sources also provides a mechanism whereby simpler games might compose to form more complex games. Along the way, I consider (...) how an old game might be appropriated to a new context by reinforcement on successful associations between old and new saliences. (shrink)

We consider how cue-reading, sensory-manipulation, and signaling games may initially evolve from ritualized decisions and how more complex games may evolve from simpler games by polymerization, template transfer, and modular composition. Modular composition is a process that combines simpler games into more complex games. Template transfer, a process by which a game is appropriated to a context other than the one in which it initially evolved, is one mechanism for modular composition. And polymerization is a particularly salient example of modular (...) composition where simpler games evolve to form more complex chains. We also consider how the evolution of new capacities by modular composition may be more efficient than evolving those capacities from basic decisions. (shrink)

We consider how cue-reading, sensory-manipulation, and signaling games may initially evolve from ritualized decisions and how more complex games may evolve from simpler games by polymerization, template transfer, and modular composition. Modular composition is a process that combines simpler games into more complex games. Template transfer, a process by which a game is appropriated to a context other than the one in which it initially evolved, is one mechanism for modular composition. And polymerization is a particularly salient example of modular (...) composition where simpler games evolve to form more complex chains. We also consider how the evolution of new capacities by modular composition may be more efficient than evolving those capacities from basic decisions. (shrink)

Starting with the view that methodological constraints depend upon the nature of the system investigated, a tripartite division between theoretical, semitheoretical, and empirical discoveries is made. Many nanosystems can only be investigated semitheoretically or empirically, and this aspect leads to some nanophenomena being weakly emergent. Self-assembling systems are used as an example, their existence suggesting that the class of systems that is not Kim-reducible may be quite large.

Over the past decades, self-assembly has attracted a lot of research attention and transformed the relations between chemistry, materials science and biology. The paper explores the impact of the current interest in self-assembly techniques on the traditional debate over the nature of life. The first section describes three different research programs of self-assembly in nanotechnology in order to characterize their metaphysical implications: (1) Hybridization (using the building blocks of living systems for making devices and machines) ; (2) Biomimetics (making artifacts (...) mimicking nature); (3) Integration (a composite of the two previous strategies). The second section focused on the elusive boundary between self-assembly and self-organization tries to map out the various positions adopted by the promoters of self-assembly on the issue of vitalism. (shrink)

Despite its biological importance, the mechanism of formation of cutin, the polymeric matrix of plant cuticles, has not yet been fully clarified. Here, for the first time, we show the participation in the process of lipid vesicles formed by the self‐assembly of endogenous polyhydroxy fatty acids. The accumulation and fusion of these vesicles (cutinsomes) at the outer part of epidermal cell wall is proposed as the mechanism for early cuticle formation. BioEssays 30:273–277, 2008. © 2008 Wiley Periodicals, Inc.

The philosophical foundations of the theory of molecular self-organization (TMS) are reconstructed and compared with the explicit methodological statements made by occasions by its author(s). Special attention is paid to those philosophical fundamentals of TMS which can turn out helpful in answering the question evoking vivid discussions in the philosophy of nature of the recent decades: whether it is possible to search for a physico-chemical explanation of the genesis of life and at the same time defend its specific character. (...) In other words: do the latest findings in self-organization of prebiological molecules allow to overcome the traditional disjunction “either physics or evolution” and to replace it with the conjunction “physics and evolution”? (shrink)

Recently, Gao et al. and Chappie et al. elucidated the crystal structures of the polytetrameric stalk domain of the dynamin‐like virus resistance protein, MxA, and of the G‐domain dimer of the large, membrane‐deforming GTPase, dynamin, respectively. Combined, they provide a hypothetical oligomeric structure for the complete dynamin protein. Here, it is discussed how the oligomers are expected to form and how they participate in dynamin mediated vesicle fission during the process of endocytosis. The proposed oligomeric structure is compared with the (...) novel mechanochemical model of dynamin function recently proposed by Bashkirov et al. and Pucadyil and Schmid. In conclusion, the new model of the dynamin oligomer has the potential to explain how short self‐limiting fissogenic dynamin assemblies are formed and how concerted GTP hydrolysis is achieved. The oligomerisation of two other dynamin superfamily proteins, the guanylate binding proteins (GBPs) and the immunity‐related GTPases (IRGs), is addressed briefly. (shrink)

We study a new variant of the dissipative particle dynamics (DPD) model that includes the possibility of dynamically forming and breaking strong bonds. The emergent reaction kinetics may then interact with self-assembly processes. We observe that self-assembled amphiphilic aggregations such as micelles have a catalytic effect on chemical reaction networks, changing both equilibrium concentrations and reaction frequencies. These simulation results are in accordance with experimental results on the so-called “concentration effect”.

I consider how complex logical operations might self-assemble in a signalling-game context via composition of simpler underlying dispositions. On the one hand, agents may take advantage of pre-evolved dispositions; on the other hand, they may co-evolve dispositions as they simultaneously learn to combine them to display more complex behaviour. In either case, the evolution of complex logical operations can be more efficient than evolving such capacities from scratch. Showing how complex phenomena like these might evolve provides an additional path to (...) the possibility of evolving more or less rich notions of compositionality. This helps provide another facet of the evolutionary story of how sufficiently rich, human-level cognitive or linguistic capacities may arise from simpler precursors. 1Signalling and Self-assembly2Simple Unary Logic Games3Composing Unary Functions for Binary Inputs 3.1Utilizing pre-evolved dispositions3.2Co-evolving logical dispositions3.3Learning appropriate outputs3.4Taking account of the full state-space of unary games3.5Role-free composition4Discussion 4.1Efficacy and efficiency of learning complex dispositions4.2Other binary operations4.3To infinity and beyond5Conclusion. (shrink)

Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical (...) stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to “self‐organization,” as often suggested, but rather to a process of genetically encoded self‐assembly where genetic programs encode and control the emergence of biological structures. (shrink)

There is growing recognition of the need to understand societal impacts of nanotechnology. Global interest in nanotechnology implies many nations will see a need to seek out advantages for military use. Militarization will inevitably include consideration of both offensive and defensive goals. This presents emerging implications for military forces in the near future, and will greatly influence the nature of warfare and peacekeeping in the distant future. The development of nanotechnology creates possibilities for both beneficial opportunities and adverse consequences as (...) a result of application to the military strategies of both large and small nations.The promise of nanotechnology for military and security roles derives from several innate characteristics. For example, further improvements in sensors are expected and already there are numerous reports of successful developments in research and development. Material properties can be tailored on a fine scale through nanomachining, scanning force microscopy, molecular self-assembly, and other techniques. (shrink)

Although many active scientists deplore the publicity about Drexler's futuristic scenario, I will argue that the controversies it has generated are very useful, at least in one respect. They help clarify the metaphysical assumptions underlying nanotechnologies, which may prove very helpful for understanding their public and cultural impact. Both Drexler and his opponents take inspiration from living systems, which they both describe as machines. However there is a striking contrast in their respective views of molecular machineries. This paper based (...) on semipopular publications is an attempt to characterize the rival models of nanomachines and to disentangle the worldviews underpinning the uses of biological reference on both sides. Finally, in an effort to point out the historical roots of the contrast in the concepts of nanomachines, I raise the question of a divide between two cultures of nanotechnology. (shrink)

Systems Biology and the Modern Synthesis are recent versions of two classical biological paradigms that are known as structuralism and functionalism, or internalism and externalism. According to functionalism (or externalism), living matter is a fundamentally passive entity that owes its organization to external forces (functions that shape organs) or to an external organizing agent (natural selection). Structuralism (or internalism), is the view that living matter is an intrinsically active entity that is capable of organizing itself from within, with purely internal (...) processes that are based on mathematical principles and physical laws. At the molecular level, the basic mechanism of the Modern Synthesis is molecular copying, the process that leads in the short run to heredity and in the long run to natural selection. The basic mechanism of Systems Biology, instead, is self-assembly, the process by which many supramolecular structures are formed by the spontaneous aggregation of their components. In addition to molecular copying and self-assembly, however, molecular biology has uncovered also a third great mechanism at the heart of life. The existence of the genetic code and of many other organic codes in Nature tells us that molecular coding is a biological reality and we need therefore a framework that accounts for it. This framework is Code biology, the study of the codes of life, a new field of research that brings to light an entirely new dimension of the living world and gives us a completely new understanding of the origin and the evolution of life. (shrink)

The autophagy initiation complex is brought about via a highly ordered and stepwise assembly process. Two crucial signaling molecules, mTORC1 and AMPK, orchestrate this assembly by phosphorylating/dephosphorylating autophagy‐related proteins. Activation of Atg1 followed by recruitment of both Atg9 vesicles and the PI3K complex I to the PAS (phagophore assembly site) are particularly crucial steps in its formation. Ypt1, a small Rab GTPase in yeast cells, also plays an essential role in the formation of the autophagy initiation complex through multiple regulatory (...) pathways. In this review, our primary focus is to discuss how signaling molecules initiate the assembly of the autophagy initiation complex, and highlight the significant roles of Ypt1 in this process. We end by addressing issues that need future clarification. (shrink)

We demonstrate a method for optimizing desired functionality in real complex chemical systems, using a genetic algorithm. The chemical systems studied here are mixtures of amphiphiles, which spontaneously exhibit a complex variety of self-assembled molecular aggregations, and the property optimized is turbidity. We also experimentally resolve the fitness landscape in some hyper-planes through the space of possible amphiphile formulations, in order to assess the practicality of our optimization method. Our method shows clear and significant progress after testing only 1 (...) % of the possible amphiphile formulations. (shrink)

Our aim in this article is to attempt to discuss propagating organization of process, a poorly articulated union of matter, energy, work, constraints and that vexed concept, “information”, which unite in far from equilibrium living physical systems. Our hope is to stimulate discussions by philosophers of biology and biologists to further clarify the concepts we discuss here. We place our discussion in the broad context of a “general biology”, properties that might well be found in life anywhere in the cosmos, (...) freed from the specific examples of terrestrial life after 3.8 billion years of evolution. By placing the discussion in this wider, if still hypothetical, context, we also try to place in context some of the extant discussion of information as intimately related to DNA, RNA and protein transcription and translation processes. While characteristic of current terrestrial life, there are no compelling grounds to suppose the same mechanisms would be involved in any life form able to evolve by heritable variation and natural selection. In turn, this allows us to discuss at least briefly, the focus of much of the philosophy of biology on population genetics, which, of course, assumes DNA, RNA, proteins, and other features of terrestrial life. Presumably, evolution by natural selection—and perhaps self-organization—could occur on many worlds via different causal mechanisms. Here we seek a non-reductionist explanation for the synthesis, accumulation, and propagation of information, work, and constraint, which we hope will provide some insight into both the biotic and abiotic universe, in terms of both molecular self reproduction and the basic work energy cycle where work is the constrained release of energy into a few degrees of freedom. The typical requirement for work itself is to construct those very constraints on the release of energy that then constitute further work. Information creation, we argue, arises in two ways: first information as natural selection assembling the very constraints on the release of energy that then constitutes work and the propagation of organization. Second, information in a more extended sense is “semiotic”, that is about the world or internal state of the organism and requires appropriate response. The idea is to combine ideas from biology, physics, and computer science, to formulate explanatory hypotheses on how information can be captured and rendered in the expected physical manifestation, which can then participate in the propagation of the organization of process in the expected biological work cycles to create the diversity in our observable biosphere. Our conclusions, to date, of this enquiry suggest a foundation which views information as the construction of constraints, which, in their physical manifestation, partially underlie the processes of evolution to dynamically determine the fitness of organisms within the context of a biotic universe. (shrink)

What makes a cell? How are cells able to replicate themselves in a stable manner? How did cellular life emerge on our planet? The answer to these fundamental questions lies at the base of biology. Cellular life is the basic unit of living organization and defines the presence of a stable information reservoir connected through the external world by a well-defined boundary. Inside the cell, chains of computations and chemical reactions take place, sustained by self-assembled molecular machines. At the (...) cell membrane, the environment and the cell communicate with each other through proteins that are able to detect small concentration changes and send the appropriate signals. But modern cells are very sophisticated entities and extracting the logic of cell organization from them is a gigantic effort. In order to answer these questions, we need to look at cells in a more basic level: a reduction of complexity is needed. Protocells, roughly defined as the simplest instances of autonomous cell-like structures, have been a matter of exploration for decades. Although most of the original work in this area was largely theoretical, the end of the twentieth century was marked by very active experimental research on minimal cells. One approach has been the top-down strategy, where living organisms (the simplest life forms) are being selectively modified to reduce their genome complexity. Such a minimal genome would be the smallest one able to sustain reproduction and growth under a given set of external constraints (mainly available molecules). The second approach is the bottom-up one, very much in the tradition of research into the origins of life. Under this approach, extremely simple life forms are built from basic chemical components, including lipids and a basic.. (shrink)

I present here a personal perspective on more than three decades of research into the structural biology of the insulin–receptor interaction. The solution of the three‐dimensional structure of insulin in 1969 provided a detailed understanding of the insulin surfaces involved in self‐assembly. In subsequent years, hundreds of insulin analogues were prepared by insulin chemists and molecular biologists, with the goal of relating the structure to the biological function of the molecule. The design of methods for direct receptor‐binding studies (...) in the 1970s, and the cloning of the receptor in the mid 1980s, provided the required tools for detailed structure–function studies. In the absence of a full three‐dimensional structure of the insulin–receptor complex, I attempt to assemble the existing pieces of the puzzle generated by our and other laboratories, in order to generate a plausible mechanistic model of the insulin–receptor interaction that explains its kinetics and negative cooperativity. BioEssays 26:1351–1362, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as based on some kind of combinatorial receptor codes. GPCRs can in fact transduce signals from the external milieu by modifying the activity of such intracellular proteins as adenylyl cyclases, phospholipases and ion channels via interactions with specific G-proteins. However, in spite (...) of the number of cell functions they can actually control, both GPCRs and their associated signal transduction pathways are extremely well conserved, for only a few alleles with null or minor functional alterations have so far been found. This would seem to suggest that, beside a mechanism for DNA repairing, there must be another level of quality control that may help maintaining GPCRs rather stable throughout evolution. We propose here receptor oligomerization to be a basic molecular mechanism controlling GPCRs redundancy in many different cell types, and the plasma membrane as the first hierarchical cell structure at which selective categorical sensing may occur. Categorical sensing can be seen as the cellular capacity for identifying and ordering complex patterns of mixed signals out of a contextual matrix, i.e., the recognition of meaningful patterns out of ubiquitous signals. In this context, redundancy and degeneracy may appear as the required feature to integrate the cell system into functional units of progressively higher hierarchical levels. (shrink)

The central dogma of molecular biology dictates that, with only a few exceptions, information proceeds from DNA to protein through an RNA intermediate. Examining the enigmatic steps from prebiotic to biological chemistry, we take another road suggesting that primordial peptides acted as template for the self-assembly of the first nucleic acids polymers. Arguing in favour of a sort of archaic “reverse translation” from proteins to RNA, our basic premise is a Hadean Earth where key biomolecules such as amino acids, (...) polypeptides, purines, pyrimidines, nucleosides and nucleotides were available under different prebiotically plausible conditions, including meteorites delivery, shallow ponds and hydrothermal vents scenarios. Supporting a protein-first scenario alternative to the RNA world hypothesis, we propose the primeval occurrence of short two-dimensional peptides termed “selective amino acid- and nucleotide-matching oligopeptides” (henceforward SANMAOs) that noncovalently bind at the same time the polymerized amino acids and the single nucleotides dispersed in the prebiotic milieu. In this theoretical paper, we describe the chemical features of this hypothetical oligopeptide, its biological plausibility and its virtues from an evolutionary perspective. We provide a theoretical example of SANMAO’s selective pairing between amino acids and nucleosides, simulating a poly-Glycine peptide that acts as a template to build a purinic chain corresponding to the glycine’s extant triplet codon GGG. Further, we discuss how SANMAO might have endorsed the formation of low-fidelity RNA’s polymerized strains, well before the appearance of the accurate genetic material’s transmission ensured by the current translation apparatus. (shrink)

This essay presents a scenario of the origin of life that is based on analysis of biological architecture and mechanical design at the microstructural level. My thesis is that the same architectural and energetic constraints that shape cells today also guided the evolution of the first cells and that the molecular scaffolds that support solid-phase biochemistry in modern cells represent living microfossils of past life forms. This concept emerged from the discovery that cells mechanically stabilize themselves using tensegrity architecture (...) and that these same building rules guide hierarchical self-assembly at all size scales (Sci Amer 278:48–57;1998). When combined with other fundamental design principles (e.g., energy minimization, topological constraints, structural hierarchies, autocatalytic sets, solid-state biochemistry), tensegrity provides a physical basis to explain how atomic and molecular elements progressively self-assembled to create hierarchical structures with increasingly complex functions, including living cells that can self-reproduce. BioEssays 22:1160–1170, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

The bacterial pathogen Listeria monocytogenes displays the remarkable ability to reorganize the actin cytoskeleton within host cells as a means for promoting cell‐to‐cell transfer of the pathogen, in a manner that evades humoral immunity. In a series of events commencing with the biosynthesis of the bacterial surface protein ActA, host cell actin and many actin‐associated protein self‐assemble to from rocket‐tail structures that continually grow at sites proximal to the bacterium and depolymerize distally. Widespread interest in the underlying molecular mechanism (...) of Listeria locomotion stems from the likelihood that the dynamic remodeling of the host cell actin cytoskeleton at the cell's leading edge involves mechanistically analogous interactions. Recent advances in our understanding of these fundamental cytoskeletal rearrangements have been achieved through a clearer recognition of the central role of oligo‐proline sequence repeats present in ActA, and these findings provide a basis for inferring the role of analogous host cell proteins in the force‐producing and position‐securing steps in pseudopod and lamellipod formation at the peripheral membrane. (shrink)

In this paper, I will reread the history of molecular genetics from a psychoanalytical angle, analysing it as a case history. Building on the developmental theories of Freud and his followers, I will distinguish four stages, namely: (1) oedipal childhood, notably the epoch of model building (1943–1953); (2) the latency period, with a focus on the development of basic skills (1953–1989); (3) adolescence, exemplified by the Human Genome Project, with its fierce conflicts, great expectations and grandiose claims (1989–2003) and (...) (4) adulthood (2003–present) during which revolutionary research areas such as molecular biology and genomics have achieved a certain level of normalcy—have evolved into a normal science. I will indicate how a psychoanalytical assessment conducted in this manner may help us to interpret and address some of the key normative issues that have been raised with regard to molecular genetics over the years, such as ‘relevance’, ‘responsible innovation’ and ‘promise management’. (shrink)

Recent successes of systems biology clarified that biological functionality is multilevel. We point out that this fact makes it necessary to revise popular views about macromolecular functions and distinguish between local, physico-chemical and global, biological functions. Our analysis shows that physico-chemical functions are merely tools of biological functionality. This result sheds new light on the origin of cellular life, indicating that in evolutionary history, assignment of biological functions to cellular ingredients plays a crucial role. In this wider picture, even if (...) aggregation of chance mutations of replicator molecules and spontaneously self-assembled proteins led to the formation of a system identical with a living cell in all physical respects but devoid of biological functions, it would remain an inanimate physical system, a pseudo-cell or a zombie-cell but not a viable cell. In the origin of life scenarios, a fundamental circularity arises, since if cells are the minimal units of life, it is apparent that assignments of cellular functions require the presence of cells and vice versa. Resolution of this dilemma requires distinguishing between physico-chemical and biological symbols as well as between physico-chemical and biological information. Our analysis of the concepts of symbol, rule and code suggests that they all rely implicitly on biological laws or principles. We show that the problem is how to establish physico-chemically arbitrary rules assigning biological functions without the presence of living organisms. We propose a solution to that problem with the help of a generalized action principle and biological harnessing of quantum uncertainties. By our proposal, biology is an autonomous science having its own fundamental principle. The biological principle ought not to be regarded as an emergent phenomenon. It can guide chemical evolution towards the biological one, progressively assigning greater complexity and functionality to macromolecules and systems of macromolecules at all levels of organization. This solution explains some perplexing facts and posits a new context for thinking about the problems of the origin of life and mind. (shrink)

Microtubules are protein cylinders with functions in cell motility, signal sensing, cell organization, intracellular transport, and chromosome segregation. One of the key properties of microtubules is their dynamic architecture, allowing them to grow and shrink in length by adding or removing copies of their basic subunit, the heterodimer αβ‐tubulin. In higher eukaryotes, de novo assembly of microtubules from αβ‐tubulin is initiated by a 2 MDa multi‐subunit complex, the gamma‐tubulin ring complex (γ‐TuRC). For many years, the structure of the γ‐TuRC and (...) the function of its subunits remained enigmatic, although structural data from the much simpler yeast counterpart, the γ‐tubulin small complex (γ‐TuSC), were available. Two recent breakthroughs in the field, high‐resolution structural analysis and recombinant reconstitution of the complex, have revolutionized our knowledge about the architecture and function of the γ‐TuRC and will form the basis for addressing outstanding questions about biogenesis and regulation of this essential microtubule organizer. (shrink)