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Journal ArticleDOI

Self-reproducing catalytic micelles as nanoscopic protocell precursors

20 Oct 2021-pp 1-9
TL;DR: This article proposed that life originated in spontaneously formed catalytic lipid micelles with catalytic capabilities, which were forerunners of biopolymer-containing protocells and showed that such micells undergo compositional autocatalytic reproduction.
Abstract: Protocells at life’s origin are often conceived as bilayer-enclosed precursors of life, whose self-reproduction rests on the early advent of replicating catalytic biopolymers. This Perspective describes an alternative scenario, wherein reproducing nanoscopic lipid micelles with catalytic capabilities were forerunners of biopolymer-containing protocells. This postulate gains considerable support from experiments describing micellar catalysis and autocatalytic proliferation, and, more recently, from reports on cross-catalysis in mixed micelles that lead to life-like steady-state dynamics. Such results, along with evidence for micellar prebiotic compatibility, synergize with predictions of our chemically stringent computer-simulated model, illustrating how mutually catalytic lipid networks may enable micellar compositional reproduction that could underlie primal selection and evolution. Finally, we highlight studies on how endogenously catalysed lipid modifications could guide further protocellular complexification, including micelle to vesicle transition and monomer to biopolymer progression. These portrayals substantiate the possibility that protocellular evolution could have been seeded by pre-RNA lipid assemblies. We propose that life originated in spontaneously formed catalytic lipid micelles. Accumulating experimental evidence shows that such micelles undergo compositional autocatalytic reproduction. Lipid-first constitutes a parsimonious alternative to the RNA-first scenario.
Citations
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Journal ArticleDOI
TL;DR: Vanchurin et al. as mentioned in this paper apply the theory of learning to physically renormalizable systems in an attempt to outline a theory of biological evolution, including the origin of life, as multilevel learning.
Abstract: We apply the theory of learning to physically renormalizable systems in an attempt to outline a theory of biological evolution, including the origin of life, as multilevel learning. We formulate seven fundamental principles of evolution that appear to be necessary and sufficient to render a universe observable and show that they entail the major features of biological evolution, including replication and natural selection. It is shown that these cornerstone phenomena of biology emerge from the fundamental features of learning dynamics such as the existence of a loss function, which is minimized during learning. We then sketch the theory of evolution using the mathematical framework of neural networks, which provides for detailed analysis of evolutionary phenomena. To demonstrate the potential of the proposed theoretical framework, we derive a generalized version of the Central Dogma of molecular biology by analyzing the flow of information during learning (back propagation) and predicting (forward propagation) the environment by evolving organisms. The more complex evolutionary phenomena, such as major transitions in evolution (in particular, the origin of life), have to be analyzed in the thermodynamic limit, which is described in detail in the paper by Vanchurin et al. [V. Vanchurin, Y. I. Wolf, E. V. Koonin, M. I. Katsnelson, Proc. Natl. Acad. Sci. U.S.A. 119, 10.1073/pnas.2120042119 (2022)].

18 citations

Journal ArticleDOI
TL;DR: In this article , the authors reviewed the experimental and bioinformatics methods for single-cell research and discussed their applications in various fields and forecast the future directions for singlecell technologies.

9 citations

Journal ArticleDOI
TL;DR: This review focuses on both membrane-bounded (vesicular) protocells and minimal cells, and provides a membrane physics background which helps to understand how morphological transformations of vesicle systems might have happened and how vesicles reproduction might be coupled with metabolic reactions and information molecules.
Abstract: In contrast to ordinary condensed matter systems, "living systems" are unique. They are based on molecular compartments that reproduce themselves through (i) an uptake of ingredients and energy from the environment, and (ii) spatially and timely coordinated internal chemical transformations. These occur on the basis of instructions encoded in information molecules (DNAs). Life originated on Earth about 4 billion years ago as self-organised systems of inorganic compounds and organic molecules including macromolecules (e.g. nucleic acids and proteins) and low molar mass amphiphiles (lipids). Before the first living systems emerged from non-living forms of matter, functional molecules and dynamic molecular assemblies must have been formed as prebiotic soft matter systems. These hypothetical cell-like compartment systems often are called "protocells". Other systems that are considered as bridging units between non-living and living systems are called "minimal cells". They are synthetic, autonomous and sustainable reproducing compartment systems, but their constituents are not limited to prebiotic substances. In this review, we focus on both membrane-bounded (vesicular) protocells and minimal cells, and provide a membrane physics background which helps to understand how morphological transformations of vesicle systems might have happened and how vesicle reproduction might be coupled with metabolic reactions and information molecules. This research, which bridges matter and life, is a great challenge in which soft matter physics, systems chemistry, and synthetic biology must take joined efforts to better understand how the transformation of protocells into living systems might have occurred at the origin of life.

8 citations

Journal ArticleDOI
TL;DR: Nanocell hybrids can protect living cells by abiotic materials and possess multiple new and multiple functions such as photo, electrical, thermal, magnetic, and mechanical properties as discussed by the authors , which has helped to propel biosynthesis into a new generation of green chemistry.

8 citations

Journal ArticleDOI
TL;DR: The results showed that this two-step supramolecular approach can actualize site-specific photosensitization and minimize nonspecific phototoxicity in a general photodynamic treatment.
Abstract: The delivery and activation of photosensitizers in a specific manner is crucial in photodynamic therapy. For an antitumoral application, it can confine the photodynamic action on the cancer cells, thereby enhancing the treatment efficacy and reducing the side effects. We report herein a novel supramolecular photosensitizing nanosystem that can be specifically activated in cancer cells and tumors that overexpress epidermal growth factor receptor (EGFR). It involves the self-assembly of the amphiphilic host-guest complex of a β-cyclodextrin-conjugated phthalocyanine-based photosensitizer (Pc-CD) and a ferrocene-substituted poly(ethylene glycol) (Mn = 2000) (Fc-PEG) in aqueous media. The resulting nanosystem Pc-CD@Fc-PEG with a hydrodynamic diameter of 124-147 nm could not emit fluorescence and generate reactive oxygen species due to the self-quenching effect and the ferrocene-based quencher. Upon interactions with molecules of adamantane substituted with an EGFR-targeting peptide (Ad-QRH*) in water and in EGFR-positive HT29 and A431 cells, the ferrocene guest species were displaced, resulting in disassembly of the nanoparticles and restoration of these photoactivities. The half-maximal inhibitory concentration values were down to 1.24 μM (for HT29 cells). The nanosystem Pc-CD@Fc-PEG could also be activated in an Ad-QRH*-treated HT29 tumor in nude mice, leading to increased intratumoral fluorescence intensity and effective eradication of the tumor upon laser irradiation. The results showed that this two-step supramolecular approach can actualize site-specific photosensitization and minimize nonspecific phototoxicity in a general photodynamic treatment.

4 citations

References
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Journal ArticleDOI
TL;DR: A cell contains millions of protein molecules, which are continually being synthesized and degraded, and at homeostasis, a given species of protein is represented by a characteristic number of molecules that is kept constant within a narrow range.
Abstract: Concurrently with or shortly after their synthesis on ribosomes, numerous specific proteins are unidirectionally translocated across or asymmetrically integrated into distinct cellular membranes. Thereafter, subpopulations of these proteins need to be sorted from each other and routed for export or targeted to other intracellular membranes or compartments. It is hypothesized here that the information for these processes, termed “protein topogenesis,” is encoded in discrete “topogenic” sequences that constitute a permanent or transient part of the polypeptide chain. The repertoire of distinct topogenic sequences is predicted to be relatively small because many different proteins would be topologically equivalent—i.e., targeted to the same intracellular address. The information content of topogenic sequences would be decoded and processed by distinct effectors. Four types of topogenic sequences could be distinguished: signal sequences, stop-transfer sequences, sorting sequences, and insertion sequences. Signal sequences initiate translocation of proteins across specific membranes. They would be decoded and processed by protein translocators that, by virtue of their signal sequence-specific domain and their unique location in distinct cellular membranes, effect unidirectional translocation of proteins across specific cellular membranes. Stop-transfer sequences interrupt the translocation process that was previously initiated by a signal sequence and, by excluding a distinct segment of the polypeptide chain from translocation, yield asymmetric integration of proteins into translocation-competent membranes. Sorting sequences would act as determinants for posttranslocational traffic of subpopulations of proteins, originating in translocation-competent donor membranes (and compartments) and going to translocation-incompetent receiver membranes (and compartments). Finally, insertion sequences initiate unilateral integration of proteins into the lipid bilayer without the mediation of a distinct protein effector. Examples are given for topogenic sequences, either alone or in combination, to provide the information for the location of proteins in any of the intracellular compartments or for the asymmetric orientation of proteins and their location in any of the cellular membranes. Proposals are made concerning the evolution of topogenic sequences and the relationship of protein topogenesis to the precellular evolution of membranes and compartments.

1,199 citations

Journal Article
01 Jan 2001-Nature
TL;DR: Advances in directed evolution and membrane biophysics make the synthesis of simple living cells, if not yet foreseeable reality, an imaginable goal.
Abstract: Advances in directed evolution and membrane biophysics make the synthesis of simple living cells, if not yet foreseeable reality, an imaginable goal. Overcoming the many scientific challenges along the way will deepen our understanding of the essence of cellular life and its origin on Earth.

910 citations

Journal ArticleDOI
TL;DR: The kinetic treatment of reactions in micellar systems can be accomplished by considering them as microheterogeneous two-phase systems, and both nonpolar and polar reagents can be solubilized.
Abstract: The notion of "green chemistry " has encouraged even synthetic organic chemists to include water as a solvent. Incredible selectivities and activities can be achieved through the addition of amphiphiles with a defined structure. The morphology of supramolecular assemblies or associates formed by surfactants vary according to the temperature and concentration. As a rule, reactions are typically conducted using simple spherical aggregates, that is, micelles in the nanometer range. The strong polarity gradient present between the hydrophilic surface and the hydrophobic core of the micelle means that both nonpolar and polar reagents can be solubilized. This solubilization results in reactants becoming more concentrated within the micelle than in the surrounding water phase and leads to an acceleration of the reaction and causes selective effects. The kinetic treatment of reactions in micellar systems can be accomplished by considering them as microheterogeneous two-phase systems.

725 citations

Journal ArticleDOI
TL;DR: 1. The Sequence Space 2. The Kinetic Equations 3. How Realistic is the Kinetic Ansatz? 4. Solutions of the Rate Equations 5. Potential Functions, Optimization, and Guided Evolution 6 . Population Structures Error Threshold.
Abstract: 1. The Sequence Space 2. The Kinetic Equations 3. How Realistic is the Kinetic Ansatz? 4. Solutions of the Rate Equations 5. Potential Functions, Optimization, and Guided Evolution 6 . Population Structures Error Threshold For Quasi-species Localization 1. Error Threshold and Selective Advantage 2. Localization Threshold for Statistically Distributed Replication Rates 3. Extreme-Value Theory for Effective Superiority 4. Relaxed Error Threshold and Gene Duplication 5. Analogies to Phase Transitions Examples of Fitness Landscapes and Stationary Populations 1. Error Threshold 2. Degenerate Quasi-species and Neutral Mutants 3. Conformation-dependent Value Functions and Fitness Landscapes 4. Asymmetry of Fitness Landscapes: Apparent Guidance of Evolution

701 citations

Journal ArticleDOI
TL;DR: The main conclusions appear independent of the idealizations of the initial model, introduce a novel kind of parallel selection for peptides catalyzing connected sequences of reactions, depend upon a new kind of minimal critical complexity whose properties are definable, and suggest that the emergence of self replicating systems may be a self organizing collective property of critically complex protein systems in prebiotic evolution.

660 citations