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Protocells or synthetic cells

The most basic building block of all living things is a cell, and the human body is composed of trillions of cells.  Cell has many parts, each with a different function. In the middle of cell is nucleus which serves as the cell’s command center, It sends directions to the cell to grow, mature, divide, or die. Inside Nucleus there are large molecules called Deoxyribonucleic acid (DNA), that contains the biological instructions that make each species unique. Most of the DNA is found in the cell’s nucleus and called nuclear DNA. An organism’s complete set of nuclear DNA is called its genome.


Synthetic biology can be defined as engineering approach to biology. And it aims to re-design of natural biological systems for useful purposes as well as design and construction of new biological parts, devices, and systems.


How it does it? Any organism’s sensing, metabolic, and decision-making capabilities depend on unique sequence of DNA bases within their genome. These DNA base pair sequences determine how a cell grows and what goes on inside it or what it produces. By changing an organism’s genome sequence, we can alter these cellular functions, and thereby engineer them.


Contemporary cells are a product of nature’s evolutionary sculpting. Their fascinating complexity has inspired scientists to create analogs from synthetic and natural components using a bottom-up approach. The ultimate goal here is to assemble a fully man-made cell that displays functionality and adaptivity as advanced as that found in nature, which will not only provide insight into the fundamental processes in natural cells but also pave the way for new applications of such artificial cells.


Yet to make a living artificial cell, one first has to consider what the minimal criteria for life are. The chemoton model, developed by Tibor Gánti, is often used to describe minimal life. (2) According to his model, an entity comprising (i) a chemical boundary system, (ii) a chemical information system, and (iii) a self-reproducing chemical motor (metabolism) can be considered “alive”. Additionally, (iv) growth and reproduction are needed for survival of the species. Finally, (v) adaptivity is paramount for life’s survival in a dynamic environment. Integrating these characteristics in a single synthetic system is an ambitious yet daunting goal

Artificial cells or semisynthetic minimal cells.

In recent years, however, several groups have successfully recreated simplified characteristics of life in synthetic systems, in particular employing nano- or micrometer-sized self-assembled compartments that can encapsulate a wide variety of (macro)molecules. Such systems are usually termed artificial cells or semisynthetic minimal cells.


The notion of minimal cells refers to cellular structures that contain the minimal and sufficient complexity to still be defined as living, or at least capable to display the most important features of biological cells.


Semi-synthetic minimal cells are constructed by encapsulating the minimal number of nucleic acids, enzymes and low molecular-weight compounds inside lipid vesicles (liposomes) in order to create a cell-like system.


The ultimate target of semi-synthetic minimal cell research consists in the creation of a compartmentalized biochemical system capable of self-producing all its molecular components (including the membrane), and eventually divide. This route, in an origin of life scenario, marks the beginning of the early cell reproduction by fission mechanism.


Researchers have used bacteria to build complex synthetic cells using a living material assembly process, advancing efforts to create protocells that mimic the earliest stages and functionality of cellular life.


Protocells could shed light on the origins of cellular life and ultimately have biomedical applications such as drug delivery and biosensing. However, the field is yet to develop protocells that mimic the basic behavior of cells. How to achieve the spontaneous, bottom-up construction of artificial cells with high organizational complexity and diverse functionality remains an unanswered question.


Scientists use bacteria to build advanced synthetic cells with lifelike functionality

Researchers led by the University of Bristol, in a September 2022 article in Nature, reported to have constructed complex protocells by combining viscous microdroplets with living bacteria. As a first step, the researchers either captured bacteria within the droplets or trapped them on the surface. Destroying the bacteria released cellular components, either on the surface or in the microdroplets, to create membrane-coated bacteriogenic protocells. The scientists believe the cells could advance the field.


“Achieving high organizational and functional complexity in synthetic cells is difficult especially under close-to-equilibrium conditions. Hopefully, our current bacteriogenic approach will help to increase the complexity of current protocell models, facilitate the integration of myriad biological components, and enable the development of energized cytomimetic systems,” Stephen Mann, PhD, from the University of Bristol’s School of Chemistry and corresponding author on the paper, said in a statement.


Analysis of the protocells showed they produce adenosine triphosphate (ATP), an organic compound that provides the energy that drives processes in living cells via glycolysis and synthesizes RNA and proteins by in vitro gene expression. The findings suggested the bacterial components remained active in the cells.


Employing a series of chemical steps to remodel the structure and morphology of the protocells, the researchers condensed the bacterial DNA into a single nucleuslike structure and infiltrated the interior of the microdroplets with a cytoskeletal-like network of protein filaments and membrane-bounded water vacuoles.


The researchers then implanted living bacteria into the protocells. In doing so, the team took a step toward the construction of a synthetic cell by facilitating self-sustainable ATP production and long-term energization for glycolysis, gene expression, and cytoskeletal assembly. Can Xu, PhD, first author on the paper, discussed the implications of the work.


“Our living-material assembly approach provides an opportunity for the bottom-up construction of symbiotic living/synthetic cell constructs. For example, using engineered bacteria it should be possible to fabricate complex modules for development in diagnostic and therapeutic areas of synthetic biology as well as in biomanufacturing and biotechnology in general,” Xu said.



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