All modern life is cellular, but how life became cellular remains uncertain. New research suggests that chemical compounds likely to be abundant on primitive earth may have contributed to the genesis of biological cellularity.

Photo credit: Tony Z. Jia

All modern life is made up of cells, from unicellular bacteria to more complex organisms like humans, which can contain billions or even trillions of cells. How life became cells, however, remains uncertain. New research led by specially appointed Assistant Professor Tony Z. Jia at the Earth-Life Science Institute (ELSI) of the Tokyo Institute of Technology, as well as from colleagues from around the world (Japan, Malaysia, France, Czech Republic, India and USA). shows that simple chemical compounds known as hydroxy acids, likely common on primitive earth, combine spontaneously to form structures reminiscent of modern cells when dried out of solution, such as on or in old beaches or Puddles can have happened. The resulting structures may have helped establish biological cellularity and offer scientists a new way to study early protobiological evolution and the origins of life itself.

Modern cells are very complex, precisely organized assemblies of millions of molecules that are precisely aligned and help move materials in and out of cells in a highly coordinated manner. Similarly, a city is not just a random collection of buildings, streets, and traffic lights. In an optimized city, the streets are laid out to allow easy access to the buildings and the flow of traffic is controlled so that the whole system works efficiently. As much as cities are the result of a historical and evolutionary process when primitive roving bands of people settled down to work together in larger groups, cells are likely the result of similar processes in which simple molecules worked together into synchronized molecular systems.

How cellularization came about is a long-standing scientific problem, and scientists are trying to understand how simple molecules can form the boundary structures that could have defined the boundaries of primitive cells. The boundaries of modern cells are typically made up of lipids, which are themselves made up of molecules that have the molecularly unusual property of spontaneously forming bounded structures in water known as vesicles. Vesicles are made up of simple molecules known as “amphiphiles”. This word comes from the Greek and means “to love both” to reflect that such molecules tend to organize with both water and themselves. This molecular dance causes these molecules to orient themselves in such a way that some of these molecules align themselves preferentially with the water in which they are dissolved and some of these molecules tend to align with one another. This type of self-organizing phenomenon is observed when groups of people enter elevators: instead of everyone looking in random directions, people in elevators tend to all orient themselves towards the elevator door for various reasons. In the experiments studied by Jia and colleagues, the low molecular weight hydroxy acid molecules, when assembled, form a new type of polymer (which might resemble amphiphiles) and form droplets rather than the bag-like structures that biological lipids have.

Modern cell boundaries, or membranes as they are called, are mainly made up of a few types of amphiphilic molecules, but scientists suggest that the property of forming a membrane is a more general property of many types of molecules. Just as modern cities have likely adapted roads, buildings, and traffic controls to cope with the subsequent issues of dealing with pedestrian, horse, and automobile traffic, primitive cells may also have slowly changed their composition and function to adapt to changes in manner How other biological substances are used functions developed. This new work offers insights into the problems that primitive emergent biological systems may have become accustomed to.

The types of molecules that help modern cells create their boundaries are only a small subset of the types that could enable this type of spontaneous self-organizing behavior. Previously, Jia and colleagues showed that hydroxy acids can easily be linked together to form larger molecules with emergent amphiphilic and self-assembling properties. They show in their new work that the subtle addition of another type of subtly different hydroxy acid, in this case one with a positive electrical charge, to the starting pool of reactants can lead to new types of polyesters that spontaneously self-assemble into more unexpected types of cell-like structures and gives them new functions that can help explain the origins of biological cellularity.

The novel structures that Jia and co-workers have created show new functions such as the ability to separate nucleic acids, which are essential for the inheritance of heredity in modern cells, or the ability to emit fluorescent light. It is important that such minor changes in chemical complexity can lead to significant functional changes. Jia and colleagues suggest that by further increasing the chemical complexity of their experimental system, even more emergent functions could arise among the resulting primitive compartments that could lead to a better understanding of the ascension of the first cells.

Jia notes that this work is not only relevant theoretically or even for basic research. Major COVID vaccines like those developed by Moderna and Pfizer include the dispersion of RNA molecules in metabolizable lipid droplets; The systems that Jia and coworkers developed could be similarly biodegradable in vivoand thus polyester droplets similar to those who made them could be useful for similar drug delivery applications.



Tony Z. Jia1.4 *Niraja V. Bapat1.2, Ajay Verma2, Irena Mamajanov1H. James Cleaves II1,3,4, Kuhan Chandru5.6 *, Incorporation of basic α-hydroxy acid residues into primitive polyester microdroplets for RNA segregation, Biomacromolecules, DOI: 10.1021 / acs.biomac.0c01697

1. Earth Life Science Institute, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8550, Japan

2. Department of Biology, Indian Institute for Science Education and Research, Pune, Maharashtra 411008, India

3. Institute for Advanced Studies, 1 Einstein Drive, Princeton, New Jersey 08540, USA

4. Blue Marble Space Institute for Science, Seattle, Washington 98154, USA

5. Institute of Physical Chemistry, University of Chemistry and Technology, Prague, Technicka 5, 16628 Prague 6 – Dejvice, Czech Republic

6. Space Research Center (ANGKASA), Climate Change Institute, National University of Malaysia, UKM, Bangi, Selangor Darul Ehsan 43650, Malaysia

More information:

Tokyo Institute of Technology (Tokyo Tech) is at the forefront of research and higher education as the leading university of science and technology in Japan. Tokyo Tech researchers excel in areas that range from materials science to biology, computer science and physics. Tokyo Tech was founded in 1881 and is home to over 10,000 undergraduate and graduate students annually who develop into scientific leaders and some of the most sought-after engineers in the industry. The Tokyo Tech Community embodies the Japanese philosophy of “Monotsukuri,” which means “technical ingenuity and innovation,” and strives to contribute to society through impactful research.

The Earth-Life Science Institute (ELSI) is one of World Premiere International’s ambitious research centers in Japan, whose aim is to advance advances in largely interdisciplinary scientific fields by inspiring the world’s greatest minds to come to Japan and collaborate on the toughest scientific problems. The main aim of ELSI is to investigate the origin and the joint development of the earth and life.

The World Premier International Research Center (WPI) initiative was founded in 2007 by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to support the construction of globally visible research centers in Japan. These institutes promote high research standards and outstanding research environments that attract top researchers from around the world. These centers are very autonomous and enable them to revolutionize the conventional ways of conducting and managing research in Japan.


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