Biological systems serve as examples for the simplified artificial systems used to create synthetic cells.
Beeld Willy Arisky via Pexels
One of the more amusing questions creationists keep asking is how did 'life' come from non-life? Or more dogmatically, they claim 'life' from 'non-life' is impossible.
They then scuttle off to hide when asked to define, 'life' and state how it can be measured to assess whether something like a rock, a bacterium or a bowl of chicken soup has any life in it. It causes the same tactic of avoidance when asked to explain how dead food becomes living tissues during the process of digestion and metabolism, if that's impossible?
The problem is creationists have been brainwashed into thinking that 'life' is something magical; some special force that turns inorganic chemicals into 'living' structures. In fact, 'life' is a process involving atoms and molecules doing their chemistry according to the fundamental laws of chemistry and physics. And the function of the process is to manage entropy - the tendency of a system to become disordered - using the energy in nutrients.
And rather than 'life' being something magical which is magically inserted into a developing embryo at some unspecified day of its development from a zygote to a free-living organism, it's actually a continuation of the life processes of the egg and sperm that united to form the zygote. There never is a 'new life', just a continuation of the parent's entropy management process.
Can 'life' be described as a process for managing entropy? Yes, describing life as a process for managing entropy is insightful and aligns with many fundamental principles of biophysics and thermodynamics.The atoms of carbon, nitrogen, oxygen, hydrogen, sulphur, phosphorus, calcium, etc. that make up the proteins, carbohydrates, fats and DNA in our cells are exactly the same as the atoms in carbon dioxide or the calcium carbonate in chalk; the nitrogen in the atmosphere or the sulphur and phosphorus in the sulfates and phosphates in the soil and rocks. They are simply chemically bonded in different combinations.
In thermodynamic terms, all systems tend toward increasing entropy, or disorder, over time (the Second Law of Thermodynamics). Living systems, however, seem to defy this by creating and maintaining highly ordered structures. To do this, they must continually manage and counteract entropy through various energy-driven processes. Here’s how life can be seen as a process of entropy management:
- Importing Energy and Exporting Entropy
- Living organisms maintain low internal entropy by importing energy from their environment (like sunlight for plants or food for animals) and then converting it into usable forms, such as ATP.
- As organisms metabolize energy, they generate heat and waste, which they expel back into the environment. This process increases entropy outside the system (in the environment), thus compensating for the local decrease in entropy within the organism.
- This exchange enables organisms to stay in a state of low entropy (highly ordered and functional) without violating the overall principle of increasing entropy in the universe.
- Self-Organization and Structural Complexity
- Life's structural organization — from molecules to cells to tissues — allows it to manage entropy within a defined boundary. Through self-assembly and self-organization, living systems can use energy to create intricate structures that serve specific functions (e.g., cell membranes, organelles).
- This organization is dynamic, as organisms are not static entities; they constantly undergo turnover at the molecular level, replacing old molecules with new ones in a tightly regulated process to maintain order.
- Homeostasis as Entropy Control
- Homeostasis can be viewed as a mechanism to control entropy within a living system. Organisms actively regulate temperature, pH, and other variables, countering the natural drift toward disorder.
- By constantly adjusting these internal conditions, life resists entropy-driven breakdowns and maintains the functionality of vital biochemical processes.
- Reproduction and Genetic Information
- Reproduction and genetic replication also play a role in entropy management. By passing genetic information to the next generation, organisms create new low-entropy systems from high-entropy components (e.g., raw molecules from the environment).
- Mutation and adaptation during reproduction introduce variability that fuels evolution, which allows life to adapt to external changes, continuously countering the entropic forces that challenge survival.
- Evolutionary Adaptation and Entropy
- Over generations, evolutionary adaptation can be seen as a long-term entropy management strategy. Species evolve in ways that increase their chances of survival within a given environment, effectively stabilizing their internal entropy levels against external pressures.
- This process leverages random mutations (which increase entropy) to occasionally produce more organized, entropy-resistant forms, which persist through natural selection.
Life as an Open Thermodynamic System
- Life operates as an *open thermodynamic system*, meaning it exchanges matter and energy with its surroundings. By constantly importing energy and exporting entropy (e.g., in the form of waste and heat), living organisms can sustain order internally.
- This perspective is particularly supported by physicist Erwin Schrödinger's famous book *What is Life?* where he proposed that life “feeds on negative entropy” (negentropy) — effectively, life extracts order from its surroundings to resist its own entropic decay.
Implications of Life as Entropy Management
- This view suggests that life’s unique feature isn’t the absence of entropy increase, but the *strategic delay* of entropy’s effects through a continual flow of energy, self-repair, and self-replication.
- It also helps explain the distinction between living and non-living entities: while non-living systems may become ordered through external processes (e.g., crystals forming), they don’t actively manage or counteract entropy in the directed, sustained way that life does.
In this way, life can indeed be framed as a sophisticated process for managing entropy, balancing the increase of disorder externally with the maintenance of order internally — a balancing act that is central to the phenomenon we recognize as "living."
Now a group of scientists led by Bert Poolman, Professor of Biochemistry at the University of Groningen, together with colleagues and researchers at six Dutch research institutes have been working to create a synthetic cell which will build a living cell from non-living chemicals. Their work is explained in a University of Groningen news release and in two papers published open access in Nature Nanotechnology and Nature Communications respectively.
Creating a simplified form of life
Scientists build modules for synthetic cell
It is one of the most fundamental questions in science: how can lifeless molecules come together to form a living cell? Bert Poolman, Professor of Biochemistry at the University of Groningen, has been working on this problem for over twenty years. He aims to understand life by trying to reconstruct it; he is building simplified artificial versions of biological systems that can be used as components for a synthetic cell. Poolman recently published two papers in Nature Nanotechnology and Nature Communications . In the first paper, he describes a system for energy conversion and cross-feeding of products of this reaction between synthetic cells, while he describes a system for concentrating and converting nutrients in cells in the second paper.
Six Dutch research institutes are collaborating in the consortium BaSyc (Building a Synthetic Cell) to build the elements needed for a synthetic cell. Poolman’s group has been working on energy conversion. The real-life equivalents he aims to replicate are mitochondria, the ‘energy factories’ of the cell. These use the molecule ADP to produce ATP, which is the standard ‘fuel’ that cells require to function. When ATP is converted back into ADP, the energy is released and used to drive other processes.
Mitochondria are the energy factories of the body.Illustration Poolman lab
Artificial mitochondria simulating the working of these little energy factories.Illustration Poolman lab
Artificial energy factories
‘Instead of the hundreds of components of mitochondria, our system for energy conversion uses just five,’ says Poolman. ‘We set out to simplify it as much as possible.’ This may sound odd, as evolution has done a great job of producing functional systems. ‘However, evolution is a one-way street, it builds on existing components and this often makes the outcome very complex,’ explains Poolman. An artificial replica, on the other hand, can be designed with a specific outcome in mind.
The five components were placed inside vesicles, tiny cell-like sacs, that can absorb ADP as well as the amino acid arginine from the surrounding fluid. The arginine is ‘burned’ (deaminated) and thus provides the energy to produce ATP, which is secreted from the vesicle. ‘Of course, the simplification comes at a price: we can only use arginine as the energy source, while cells use all kinds of different molecules, such as amino acids, fats, and sugars.’
Next, the Poolman group designed a second vesicle that is able to absorb the secreted ATP and use it to drive an energy-consuming reaction. The energy is provided by turning ATP back into ADP, which is then secreted and can be absorbed by the first vesicle, closing the loop. Such a cycle of ATP production and use is the foundation of metabolism in every living cell and drives the ‘machinery’ for energy-consuming reactions such as growth, cell division, protein synthesis, DNA replication, and more.
An artificial pumping system
The cells of our muscles are also powered by ATP.Photo Victor Freitas
The second module that Poolman created was a bit different: a vesicle in which a chemical process causes the interior to build up a negative charge and, in doing so, form an electrical potential, similar to that of an electronic circuit. The electrical potential is used to couple charge movement to the accumulation of nutrients inside the vesicle, which is carried out by transporters. These proteins in the membrane of the vesicle work a bit like a water wheel: positively charged protons ‘flow’ through it from outside the vesicle to the negatively charged interior. This flow drives the transporter, which in this case imports a sugar molecule, lactose. Again, this is a very common process in living cells, requiring many components that Poolman and his team mimicked with just two components.
When he submitted a paper describing this system, a reviewer asked if he couldn’t do something with the lactose that is being transported, as cells use nutrients like this to produce useful building blocks. Poolman took up the challenge and added three more enzymes to the system, which oxidized the sugar and enabled the production of the coenzyme NADH. ‘This helper molecule plays an essential role in the proper functioning of all cells,’ explains Poolman. ‘And by adding NADH production, we have shown that it is feasible to expand the system.’
But what about the synthetic cell?
A simplified synthetic equivalent of a cell would be like a blueprint for life.Image EVOLF project
Having a simplified synthetic equivalent of two key features of life is fascinating, but many more steps need to be integrated to form an autonomously growing and dividing synthetic cell. ‘The next step we want to take is adding our metabolic energy producing systems to a synthetic cell division system created by colleagues,’ says Poolman.
The BaSyc programme is entering its final years; funding for a new programme has recently been secured. A large consortium of Dutch groups, in which Poolman is one of the leading scientists, received 40 million euros to create life from non-living modules. This EVOLF project is set to run for another ten years and aims to find out how many more lifeless modules can come together and create living cells. ‘Ultimately, this would give us a blueprint for life, something that is currently lacking in biology,’ concludes Poolman. ‘This may eventually have all kinds of applications, but will also help us to better understand what life is.’
Publications:Miyer F. Patiño-Ruiz, Zaid Ramdhan Anshari, Bauke Gaastra, Dirk J. Slotboom & Bert Poolman:
Chemiosmotic nutrient transport in synthetic cells powered by electrogenic antiport coupled to decarboxylation Nature Communications, 12 September 2024
Laura Heinen, Marco van den Noort, Martin S. King, Edmund R.S. Kunji and Bert Poolman:
Synthetic syntrophy: Synthetic syntrophy for adenine nucleotide cross-feeding between metabolically active nanoreactors Nature Nanotechnology 21 October 2024.
Abstract
Living systems depend on continuous energy input for growth, replication and information processing. Cells use membrane proteins as nanomachines to convert light or chemical energy of nutrients into other forms of energy, such as ion gradients or adenosine triphosphate (ATP). However, engineering sustained fuel supply and metabolic energy conversion in synthetic systems is challenging. Here, inspired by endosymbionts that rely on the host cell for their nutrients, we introduce the concept of cross-feeding to exchange ATP and ADP between lipid-based compartments hundreds of nanometres in size. One population of vesicles enzymatically produces ATP in the mM concentration range and exports it. A second population of vesicles takes up this ATP to fuel internal reactions. The produced ADP feeds back to the first vesicles, and ATP-dependent reactions can be fuelled sustainably for up to at least 24 h. The vesicles are a platform technology to fuel ATP-dependent processes in a sustained fashion, with potential applications in synthetic cells and nanoreactors. Fundamentally, the vesicles enable studying non-equilibrium processes in an energy-controlled environment and promote the development and understanding of constructing life-like metabolic systems on the nanoscale.
Heinen, L., van den Noort, M., King, M.S. et al.
Synthetic syntrophy for adenine nucleotide cross-feeding between metabolically active nanoreactors. Nat. Nanotechnol. (2024). https://doi.org/10.1038/s41565-024-01811-1
Copyright: © 2024 The authors.
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
AbstractI wonder if and when we are going to see creationists drop yet another claim in view of the scientific evidence that they are wrong when they claim science can't create 'life' from 'non-life', like they had to stop claiming that evolution was impossible due to the Second Law of Thermodynamics, that Earth is at the center of the Universe and doesn't move in space and that the sun, moon and stars are stuck to a dome over a small flat earth. It normally takes a few decades at least for creationists to realise that they got it wrong again.
Cellular homeostasis depends on the supply of metabolic energy in the form of ATP and electrochemical ion gradients. The construction of synthetic cells requires a constant supply of energy to drive membrane transport and metabolism. Here, we provide synthetic cells with long-lasting metabolic energy in the form of an electrochemical proton gradient. Leveraging the L-malate decarboxylation pathway we generate a stable proton gradient and electrical potential in lipid vesicles by electrogenic L-malate/L-lactate exchange coupled to L-malate decarboxylation. By co-reconstitution with the transporters GltP and LacY, the synthetic cells maintain accumulation of L-glutamate and lactose over periods of hours, mimicking nutrient feeding in living cells. We couple the accumulation of lactose to a metabolic network for the generation of intermediates of the glycolytic and pentose phosphate pathways. This study underscores the potential of harnessing a proton motive force via a simple metabolic network, paving the way for the development of more complex synthetic systems.
Patiño-Ruiz, M.F., Anshari, Z.R., Gaastra, B. et al.
Chemiosmotic nutrient transport in synthetic cells powered by electrogenic antiport coupled to decarboxylation. Nat Commun 15, 7976 (2024). https://doi.org/10.1038/s41467-024-52085-z
Published by Springer Nature Ltd. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
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