Kepa Ruiz-Mirazo

Prebiotic Systems Chemistry: New Perspectives for the Origins of Life

Kepa Ruiz-Mirazo,†,∥ Carlos Briones,‡,∥ and Andreś de la Escosura* †Biophysics Unit (CSIC-UPV/EHU), Leioa, and Department of Logic and Philosophy of Science, University of the Basque Country, Avenida de Tolosa 70, 20080 Donostia−San Sebastiań, Spain ‡Department of Molecular Evolution, Centro de Astrobiología (CSIC−INTA, associated to the NASA Astrobiology Institute), Carretera de Ajalvir, Km 4, 28850 Torrejoń de Ardoz, Madrid, Spain Organic Chemistry Department, Universidad Autońoma de Madrid, Cantoblanco, 28049 Madrid, Spain

Basic autonomy as a fundamental step in the synthesis of life

In the search for the primary roots of autonomy (a pivotal concept in Varelas comprehensive understanding of living beings), the theory of autopoiesis provided an explicit criterion to define minimal life in universal terms, and was taken as a guideline in the research program for the artificial synthesis of biological systems. Acknowledging the invaluable contribution of the autopoietic school to present biological thinking, we offer an alternative way of conceiving the most basic forms of autonomy. We give a bottom-up account of the origins of self-production (or self-construction, as we propose to call it), pointing out which are the minimal material and energetic requirements for the constitution of basic autonomous systems. This account is, indeed, committed to the project of developing a general theory of biology, but well grounded in the universal laws of physics and chemistry. We consider that the autopoietic theory was formulated in highly abstract terms and, in order to advance in the implementation of minimal autonomous systems (and, at the same time, make major progress in exploring the origins of life), a more specific characterization of minimal autonomous systems is required. Such a characterization will not be drawn from a review of the autopoietic criteria and terminology ( la Fleischaker) but demands a whole reformulation of the question: a proper naturalization of the concept of autonomy. Finally, we also discuss why basic autonomy, according to our account, is necessary but not sufficient for life, in contrast with Varelas idea that autopoiesis was a necessary and sufficient condition for it.

Stochastic simulations of minimal self-reproducing cellular systems

This paper is a theoretical attempt to gain insight into the problem of how self-assembling vesicles (closed bilayer structures) could progressively turn into minimal self-producing and self-reproducing cells, i.e. into interesting candidates for (proto)biological systems. With this aim, we make use of a recently developed object-oriented platform to carry out stochastic simulations of chemical reaction networks that take place in dynamic cellular compartments. We apply this new tool to study the behaviour of different minimal cell models, making realistic assumptions about the physico-chemical processes and conditions involved (e.g. thermodynamic equilibrium/non-equilibrium, variable volume-to-surface relationship, osmotic pressure, solute diffusion across the membrane due to concentration gradients, buffering effect). The new programming platform has been designed to analyse not only how a single protometabolic cell could maintain itself, grow or divide, but also how a collection of these cells could ‘evolve’ as a result of their mutual interactions in a common environment.

Organisms and their place in biology

In this paper we review the concept of organism analysing the main ideas related to it in the context of present biological theories. The discussion is focused and developed according to four key issues: individuality, organisation, autonomy and reproduction. Once these basic connections are established, a spectrum of possible entities that fall under the label ‘organism’ is looked over, with special emphasis on limit or controversial cases. The aim is to see whether they all share a set of common features and, if they do, why it is so difficult to reach a consensus on the definition of the term. Finally, we try to release somehow the tension between those hierarchical schemes proposed to account for life as a global phenomenon and those approaches that take organisms as the central target of (theoretical) biology, suggesting a possible middle-ground solution open for further research.

Autonomy in evolution: from minimal to complex life

Our aim in the present paper is to approach the nature of life from the perspective of autonomy, showing that this perspective can be helpful for overcoming the traditional Cartesian gap between the physical and cognitive domains. We first argue that, although the phenomenon of life manifests itself as highly complex and multidimensional, requiring various levels of description, individual organisms constitute the core of this multifarious phenomenology. Thereafter, our discussion focuses on the nature of the organization of individual living entities, proposing autonomy as the main concept to grasp it. In the second part of the article we show how autonomy is also fundamental to explaining major evolutionary transitions, in an attempt to rethink evolution from the point of view of the organizational structure of the entities/organisms involved. This gives further support to the idea of autonomy not only as a key to understanding life in general but also the complex expressions of it that we observe on our planet. Finally, we suggest a possible general principle that underlies those evolutionary transitions, which allow for the open-ended redefinition of autonomous systems: namely, the relative dynamic decoupling that must be articulated among distinct parts, modules or modes of operation in these systems.

Modelling autonomy: Simulating the essence of life and cognition

The story of this special issue goes back to early 006, when we thought that it could be a good idea o organize a workshop for the ALifeX Conference Bloomington, 3–7 June 2006) on the subject of ‘Articial Autonomy’. The main goal was to analyse the tate of affairs in the field, focusing on present modlling approaches and techniques, but also reviewing ome foundational aspects of autonomy as a key concept n biological and cognitive sciences. Niels Bertschinger, nthony Chemero, John Collier, Chrisantha Fernando, akashi Ikegami, Keisuke Suzuki and ourselves conributed to it, and we were considerably satisfied with the esults, in terms of the discussions we had, the quality f the work that was presented there and the shared coniction that autonomous systems research was in need f a thorough revision, assessing previous landmarks in he field but also incorporating some very promising new pproaches. This gave us the necessary energy to engage n the project of elaborating further our contributions, utting them together and pushing a possible process f collective publication. The second important input hat made this project actually realizable came from the ditors of the journal BioSystems, who showed us very arly their interest in a collection of novel articles on he topic of autonomy. As a result, we considered that it as worth the effort organizing a second meeting in the asque country, with the aim of involving some other

Defining Life or Bringing Biology to Life

In the present, post-genomic times, systemic or holistic approaches to living phenomena are compulsory to overcome the limits of traditional strategies, such as the methodological reductionism of molecular biology. In this paper, we propose that theoretical and philosophical efforts to define life also contribute to those integrative approaches, providing a global theoretical framework that may help to deal with or interpret the huge amount of data being collected by current high-throughput technologies, in this so-called ‘omics’ revolution. We claim that two fundamental notions can capture the core of the living, (basic) autonomy and open-ended evolution, and that only the complementary combination of these two theoretical constructs offers an adequate solution to the problem of defining the nature of life in specific enough—but also encompassing enough—terms. This tentative solution should also illuminate, in its most elementary version, the leading steps towards living beings on Earth.

Modelling lipid competition dynamics in heterogeneous protocell populations

Recent experimental work in the field of synthetic protocell biology has shown that prebiotic vesicles are able to ‘steal’ lipids from each other. This phenomenon is driven purely by asymmetries in the physical state or composition of the vesicle membranes, and, when lipid resource is limited, translates directly into competition amongst the vesicles. Such a scenario is interesting from an origins of life perspective because a rudimentary form of cell-level selection emerges. To sharpen intuition about possible mechanisms underlying this behaviour, experimental work must be complemented with theoretical modelling. The aim of this paper is to provide a coarse-grain mathematical model of protocell lipid competition. Our model is capable of reproducing, often quantitatively, results from core experimental papers that reported distinct types vesicle competition. Additionally, we make some predictions untested in the lab, and develop a general numerical method for quickly solving the equilibrium point of a model vesicle population.

Emergent Chemical Behavior in Variable-Volume Protocells

Artificial protocellular compartments and lipid vesicles have been used as model systems to understand the origins and requirements for early cells, as well as to design encapsulated reactors for biotechnology. One prominent feature of vesicles is the semi-permeable nature of their membranes, able to support passive diffusion of individual solute species into/out of the compartment, in addition to an osmotic water flow in the opposite direction to the net solute concentration gradient. Crucially, this water flow affects the internal aqueous volume of the vesicle in response to osmotic imbalances, in particular those created by ongoing reactions within the system. In this theoretical study, we pay attention to this often overlooked aspect and show, via the use of a simple semi-spatial vesicle reactor model, that a changing solvent volume introduces interesting non-linearities into an encapsulated chemistry. Focusing on bistability, we demonstrate how a changing volume compartment can degenerate existing bistable reactions, but also promote emergent bistability from very simple reactions, which are not bistable in bulk conditions. One particularly remarkable effect is that two or more chemically-independent reactions, with mutually exclusive reaction kinetics, are able to couple their dynamics through the variation of solvent volume inside the vesicle. Our results suggest that other chemical innovations should be expected when more realistic and active properties of protocellular compartments are taken into account.

Ether- versus Ester-Linked Phospholipid Bilayers Containing either Linear or Branched Apolar Chains

We studied the properties of bilayers formed by ether-and ester-containing phospholipids, whose hydrocarbon chains can be either linear or branched, using sn-1,2 dipalmitoyl, dihexadecyl, diphytanoyl, and diphytanyl phosphatidylcholines (DPPC, DHPC, DPhoPC, and DPhPC, respectively) either pure or in binary mixtures. Differential scanning calorimetry and confocal fluorescence microscopy of giant unilamellar vesicles concurred in showing that equimolar mixtures of linear and branched lipids gave rise to gel/fluid phase coexistence at room temperature. Mixtures containing DHPC evolved in time (0.5 h) from initial reticulated domains to extended solid ones when an equilibrium was achieved. The nanomechanical properties of supported planar bilayers formed by each of the four lipids studied by atomic force microscopy revealed average breakdown forces Fb decreasing in the order DHPC ≥ DPPC > DPhoPC >> DPhPC. Moreover, except for DPPC, two different Fb values were found for each lipid. Atomic force microscopy imaging of DHPC was peculiar in showing two coexisting phases of different heights, probably corresponding to an interdigitated gel phase that gradually transformed, over a period of 0.5 h, into a regular tilted gel phase. Permeability to nonelectrolytes showed that linear-chain phospholipids allowed a higher rate of solute + water diffusion than branched-chain phospholipids, yet the former supported a smaller extent of swelling of the corresponding vesicles. Ether or ester bonds appeared to have only a minor effect on permeability.