Special Issue "Protocells - Designs for Life"


A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Life Sciences".

Deadline for manuscript submissions: closed (31 July 2014)

Special Issue Editors

Guest Editor
Prof. Dr. Fabio Mavelli
Chemistry Department, University of Bari, Via Orabona 4, 70124 Bari
Website: http://www.chimica.uniba.it/dipartimento/personale/250-mavelli-fabio
E-Mail: fabio.mavelli@uniba.it
Interests: origins of life; emergence of life, synthetic cells; confined reactions; stochastic simulations; random fluctuation effects

Guest Editor
Dr. Pasquale Stano
Science Department, University Roma Tre, Viale G. Marconi 446, 00146 Rome
Website: http://www.plluisi.org/stano.html
E-Mail: pasquale.stano@uniroma3.it
Interests: origins of life; synthetic biology; artificial life; synthetic cells; drug delivery; bio-chem-ICTs

Special Issue Information

Dear Colleagues,

Over the last few decades, the study of liposome-based minimal cell models has gained prominence in an interdisciplinary field concerning the origins of life and synthetic biology. These models have stimulated, and continue to stimulate, a large number of scientists, whose contributions are complementary.
From an experimental point of view, several approaches are currently under scrutiny, from the semi-synthetic cell model, to one that is strictly prebiotic, to the fully synthetic one. Despite the apparent diversity in this research field, recent efforts and discoveries have collectively contributed to increasing our knowledge of the physico-chemical conditions that promoted the transition from non-living to living matter; this knowledge sheds light on the origin of early cells on earth and at the same time, enables novel advancements in synthetic cell technology that might be useful for applicative research.
On the other hand, the structure of these cell model systems, whose complexity is sufficient for displaying emergent properties (but at the same time is “minimal”), can also be studied via detailed in silico models with both deterministic and stochastic approaches. These computational studies, especially when based on realistic hypotheses or on parameters inferred by experimental data, allow for the exploration of dynamical behaviors that can be difficult to investigate experimentally. The studies can also be useful for elucidating the effects of reaction compartmentalization and the rule of random fluctuations on protocell population dynamics.
Altogether, in silico and in vitro investigations are paving the way to a novel research arena that appears to be both very rich (thanks to its intrinsic interdisciplinary character) and promising (because only via synthetic/constructive approaches is it possible to enquire about the features of simple, early cells). This approach also stimulates more theoretical considerations with respect to intriguing questions, such as “what is life?” and further supports abiogenesis as the best theoretical framework, from a scientific viewpoint, for understanding the emergence of living systems on Earth.
Therefore, the study of minimal cell models is now an exciting multidisciplinary area of research mainly aimed at identifying the physico-chemical constraints (or unexpected and helpful emerging features) that are pertinent to the organization of dynamic chemical networks inside micro-compartments. This Special Issue covers all aspects of minimal cell models(i.e., experimental and computational models). The submission of scientific perspectives, comprehensive reviews or research articles is most welcome.

Prof. Dr. Fabio Mavelli
Dr. Pasquale Stano
Guest Editors


Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.


  • artificial cells
  • autopoiesis
  • cell-free systems
  • emergence of life
  • minimal cells
  • origin of life
  • protocells
  • random fluctuations effect
  • stochastic simulations

Published Papers (10 papers)

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Displaying article 1-10
p. 214-229
by , ,  and
Life 2015, 5(1), 214-229; doi:10.3390/life5010214
Received: 30 October 2014 / Revised: 29 December 2014 / Accepted: 6 January 2015 / Published: 19 January 2015
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(This article belongs to the Special Issue Protocells - Designs for Life)
p. 181-211
by ,  and
Life 2015, 5(1), 181-211; doi:10.3390/life5010181
Received: 14 October 2014 / Accepted: 4 January 2015 / Published: 13 January 2015
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(This article belongs to the Special Issue Protocells - Designs for Life)
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p. 1092-1116
by ,  and
Life 2014, 4(4), 1092-1116; doi:10.3390/life4041092
Received: 1 October 2014 / Revised: 2 December 2014 / Accepted: 11 December 2014 / Published: 19 December 2014
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(This article belongs to the Special Issue Protocells - Designs for Life)
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p. 1038-1049
Life 2014, 4(4), 1038-1049; doi:10.3390/life4041038
Received: 31 October 2014 / Revised: 8 December 2014 / Accepted: 11 December 2014 / Published: 17 December 2014
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(This article belongs to the Special Issue Protocells - Designs for Life)
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p. 915-928
by  and
Life 2014, 4(4), 915-928; doi:10.3390/life4040915
Received: 24 October 2014 / Revised: 25 November 2014 / Accepted: 3 December 2014 / Published: 11 December 2014
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(This article belongs to the Special Issue Protocells - Designs for Life)
p. 929-943
by  and
Life 2014, 4(4), 929-943; doi:10.3390/life4040929
Received: 7 October 2014 / Revised: 21 November 2014 / Accepted: 3 December 2014 / Published: 11 December 2014
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(This article belongs to the Special Issue Protocells - Designs for Life)
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p. 837-864
by , , , ,  and
Life 2014, 4(4), 837-864; doi:10.3390/life4040837
Received: 30 August 2014 / Revised: 25 October 2014 / Accepted: 10 November 2014 / Published: 3 December 2014
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(This article belongs to the Special Issue Protocells - Designs for Life)
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p. 598-620
by  and
Life 2014, 4(4), 598-620; doi:10.3390/life4040598
Received: 18 September 2014 / Revised: 15 October 2014 / Accepted: 17 October 2014 / Published: 3 November 2014
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(This article belongs to the Special Issue Protocells - Designs for Life)
p. 586-597
by  and
Life 2014, 4(4), 586-597; doi:10.3390/life4040586
Received: 23 September 2014 / Revised: 17 October 2014 / Accepted: 22 October 2014 / Published: 29 October 2014
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(This article belongs to the Special Issue Protocells - Designs for Life)
p. 457-490
Life 2014, 4(3), 457-490; doi:10.3390/life4030457
Received: 2 August 2014 / Accepted: 25 August 2014 / Published: 5 September 2014
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Submitted Papers

Type of Paper: Review
Synthetic Biology: The Bridge between Artificial and Natural Cells
Yunfeng Ding, Fan Wu, Cheemeng Tan *
Department of Biomedical Engineering, University of California Davis, Davis, CA, USA
Artificial cells are simple cell-like entities that possess certain properties of natural cells. In general, artificial cells are constructed using three parts: (1) Biological membranes that serve as protective barriers, while allowing communication between the cells and the environment. (2) Transcription and translation machineries that synthesize proteins based on genetic sequences. (3) Genetic modules that control dynamics of the whole cell. Artificial cells are minimal and well-defined systems that can be more easily engineered and controlled when compared to natural cells. Artificial cells could be used as biomimetic systems to study and understand natural behaviors of cells with minimal interruptions from cellular complexity. However, along with our increasing understanding of natural cells, there are growing gaps between natural and artificial cells. For example, how much information can we encode into artificial cells? What is the minimal number of factors that can control or enhance gene expression? Can artificial cells communicate with their environments efficiently? Can artificial cells replicate, divide, or even evolve? We will review synthetic biological methods that could shrink the gaps between natural and artificial cells. The closure of these gaps will lead to advancements in synthetic biology, cellular biology, and biomedical applications. In this review, we will first discuss differences and similarities between natural and artificial cells. Next, we will introduce methodologies that shrink the gaps between artificial and natural cells. Specifically, we will discuss the following modules: genetic circuits that could be incorporated into artificial cells, factors that could affect gene expression, communication molecules between artificial cells and their environments, and self-replication.

Title: Membrane Permeability: The Link between Procellular Metabolism, Evolution and the Environment
Andrew Pohorille 1, Michael Wilson 2 and Chenyu Wei 2
1 NASA-Ames Research Center, Mail Stop 239-4, Moffett Field, CA 94035, USA
Department of Pharmaceutical Chemistry University of California, San Francisco USA
Permeability of protocellular membranes was inextricably connected to the metabolism they encapsulated: to be inheritable, early metabolism must have led to an increased rate of growth and division of vesicles and, similarly, transport through vesicle boundaries must have supported the evolution of metabolism. We will review how simple molecules, building blocks of biopolymers, protons and other ions permeated through ancestral membranes from the environment, and discuss how this process could couple to the emergence and evolution of metabolism. We will show that consideration of permeation imposes concrete constrains of scenarios for the origin of life.

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Active role of DNA to generated cell-sized droplet in a crowding binary polymer solution
Authors: Kanta Tsumoto, Masafumi Arai, Naoki Nacatani, Shun N. Watanabe, Kenichi Yoshikawa
Affiliation: Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, 610-0394, Japan
Abstract: In living cells, DNA molecules are stored inside microcompartments where biopolymers are highly concentrated. It is expected that structures of such organelles have been developed through the incorporation and regulation with genetic products. We report that cell-like micro-compartmentalization of DNAs is spontaneously achieved under a crowding environment with binary polymers in the presence of DNA. Actually for a crowding solution at a certain mixing ration of dextran and PEG close to the binodal curve, it is found that DNA are selectively located inside dextran-rich microdroplets. By use of optical tweezers, we will show the manipulation of the cell-sized droplet with DNA, such as fusion and deformation. We will discuss the active role of DNA to generate stable cell-sized droplet.
Keywords: DNA; dextran; polyethylene glycol (PEG); crowding; aqueous two phase system (ATPS); optical tweezers;microcompartment; microdroplet

Title: TiMesoscopic replicable protocells: bridging the abiogenesis gap
Authors: Doron Lancet and Omer Markovitch
Affiliaiton: Dept. Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel
Abstract: Protocells are often portrayed as lipid vesicles enclosing informational/catalytic biopolymers in their aqueous interior. We present an early protocellular evolution scenario, invoking heterogeneous mesoscopic micelles without biopolymeric content, simple enough for abiogenesis. Micellar small size allows the storage of copyable, variation-prone compositional information, supporting primeval selection and evolution.
Kewords: Life’s origin; lipid micelles; micellar protocells; compositional information; abiogenesis; early evolution

Title: Current ideas about prebiological compartmentalization
Authors: Pierre-Alain Monnard 1 and Peter Walde 2
Affiliaiton: 1 Center for Fundamental Living Technology (FLinT), Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230  Odense, Denmark; monnard@ifk.sdu.dk
2 Laboratory of Polymer Chemistry, Department of Materials, ETH-Zürich, Vladimir-Prelog-Weg 5, CH-8093 Zürich, Switzerland; E-Mail: peter.walde@mat.ethz.ch
Abstract: Contemporary biological cells are highly sophisticated compartment systems which separate an internal volume from the external medium though a boundary which controls in complex ways the exchange of matter and energy between the cell’s interior and the environment. Since such compartmentalization is a fundamental principle of all forms of life, scenarios have been elaborated about the emergence of prebiological compartments (protocells), in particular about their likely structural and dynamic features. Past and current protocell model systems are presented and compared.
Keywords: Protocell; compartment; lipids; fatty acids; vesicles; coacervates

Title: Entrapment of macromolecules inside lipid vesicles
Authors: Pasquale Stano and Pier Luigi Luisi et al.
Affiliation: Science Department, Roma Tre University, Viale G. Marconi 446, 00146 Roma, Italy
Abstract: One of the key mechanisms at the origin of life is the entrapment (encapsulation) of molecules—and in particular macromolecules – inside primitive cells. Here we firstly review how recent detailed studies on macromolecular entrapment in spontaneously formed lipid vesicles (liposomes) shed light on the physics of primitive cell self-assembly from separated components. Then, we discuss the relevance of these finding in origin of life scenarios whereby the spontaneous concentration of diluted molecules in lipid compartments might have driven the onset of primitive metabolism.

Title: Compartmentalized systems for efficient energy conversion
Francesco Milano 1, Roberto Rocco Tangorra 2, Peter Maroti 3 and Massimo Trotta 1
Affiliation: 1 Istituto per i Processi Chimico Fisici - CNR Bari, Italy
2 Dipartimento di Chimica Università di Bari, Italy
3 Department of Biophysiscs, University of Szeged, Hungary
Abstract: In the manuscript the basic of membrane energization will be discussed as consequence of the need of to separate inside from outside. The simplest photosynthetic enzyme, a transmembrane protein, employs the solar radiation to translocate protons from the inside. A liposomal system reconstituted with the photosynthetic protein will be used to generate a transmembrane proton gradient driven by light.

Title: From Vesicle toward Protocell: Perspective of Soft Matter Physics
Yuka Sakuma and Masayuki Imai
Department of Physics, Tohoku University, Japan
It is a great challenge to construct protocells from molecular assemblies. A milestone of this challenge is to realize vesicle dynamics relevant to the cellular functions, such as membrane traffic and self-reproduction, using simple amphiphilic molecules. The soft matter physics will play an important role to develop the vesicles having such functions. Here we show that simple binary phospholipid vesicles have potential to reproduce the relevant functions, adhesion, pore formation, and self-reproduction of vesicles, by coupling the lipid geometries (spontaneous curvatures) and the phase separation. This achievement will shed light on the pathway from the molecular assembly to the cellular life.

Last update: 12 December 2014

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