Artificial Biology: Molecular Design and Cell Mimicry

Artificial biology is a sub-discipline of biomolecular engineering that aims to mimic and/or reconstruct the structure and the function of native biomolecules and small life forms – often using non-biological building blocks. Questions that comprise the field of artificial biology are diverse. Can we design artificial enzymes and/or make inorganic or non-organic materials that perform catalysis like enzymes do, possibly in complex intracellular environments or in living organisms? Can we make molecules self-replicate? Is artificial recognition, i.e., mimicking antibody–antigen affinity or the molecular fingerprints of human cells, possible? Can we engineer compartmentalized processes that imitate the performance of our organelles inside of cells? How do we facilitate controlled transport and mobility of cargo-loaded carriers at the micro- and nanoscale? To what extent can artificial cells exchange information among each other or with their natural role models? Can we integrate artificial and biological entities into 3D tissue structure? The answer to some of these questions is ‘yes' but remains ‘probably' for others. The tools that are used on the quest to identify answers to these complex questions are originating from chemistry, physics, biology, material science and engineering. Artificial biology is a highly interdisciplinary field and products of these studies are impactful, with interest to a broad scientific readership. All of the above makes it relevant to the readership of Small. The different contributions to this Special Issue represent selected aspects of artificial biology, and all submissions underwent the regular, stringent peer-revision. The result is an exciting collection of original contributions and review articles on artificial biology, reflecting the field's inherent interdisciplinary nature. In terms of length scale, contributions cover examples of artificial biology from low nanometer to hundreds of microns in size. This Special Issue contains Reviews on protein engineering (https://doi.org/10.1002/smll.201903093), artificial glycocalyx (https://doi.org/10.1002/smll.201906890), molecularly imprinted synthetic antibodies (https://doi.org/10.1002/smll.201906644), artificial metalloenzymes (https://doi.org/10.1002/smll.202000392), and nanozymes that use endogenous substrates (https://doi.org/10.1002/smll.201907635). Further, original contributions discuss nanozymes for scavenging reactive oxygen species (https://doi.org/10.1002/smll.201902123) and to produce the natural signaling molecule nitric oxide (https://doi.org/10.1002/smll.201906744). Increasing in size and complexity, this Special Issue includes original articles that consider the development of artificial organelles in the form of theranostic nano-compartments (https://doi.org/10.1002/smll.201906492), or as functional giant unilamellar vesicles (https://doi.org/10.1002/smll.201906424). Intracellular fate of polymer–lipid hybrid vesicles was discussed with the aim to focus on structural integrity of artificial organelles (https://doi.org/10.1002/smll.201906493). Locomotion is of paramount importance in living systems. It is therefore not surprising that the assembly of artificial motile entities (often referred to as micro/nanomotors or swimmers) is fascinating science. The prime objective of these studies is to mimic the triggered, controlled and efficient transport phenomena observed in nature. This Special Issue contains Reviews that outline the recent advances in biomedical cargo transportation using micromotors (https://doi.org/10.1002/smll.201902464), that focus on biocompatibility of micromotors (https://doi.org/10.1002/smll.201906184), and on engineering micromotors that are activated by light for a variety of applications (https://doi.org/10.1002/smll.201903179). The original contributions discuss an effort on distinguishing micromotors by fluorescence (https://doi.org/10.1002/smll.201902365), light-triggered micromotors (https://doi.org/10.1002/smll.201902944), and bubble-propelled micromotors in confined space (https://doi.org/10.1002/smll.202000413). When considering the larger length scale, the assembly of artificial cells aims to address different challenges including elucidating the origin of life, understanding the complexity of the cellular machinery or engineering synthetic entities that can support their natural role models. This Special Issue contains Reviews on bottom-up assemblies that can mimic cellular behavior,(https://doi.org/10.1002/smll.201907680) and on protein encapsulation in coacervates,(https://doi.org/10.1002/smll.201907671) and a discussion on the emerging concept of ‘printing biology' that explores the combination of printing with bottom-up assembly of biomimetic structures(https://doi.org/10.1002/smll.201907691). The original articles outline the use of 3D-printed protein cages to change the shape of giant unilamellar vesicles (https://doi.org/10.1002/smll.201906259), and the arrangement of amphiphilic polymers in GUVs (https://doi.org/10.1002/smll.201905230). Further, vesicles made from cyclophospholipid and fatty alcohol are presented to be resilient to metal ions, which is an anticipated prerequisite for protocells in early Earth environment (https://doi.org/10.1002/smll.201903381). In addition, the rudimentary communication between enzyme-loaded giant unilamellar vesicles and red blood cells is discussed (https://doi.org/10.1002/smll.201906394). This Special Issue was put together with the prospect of hosting an international conference on ‘Artificial biology: Molecular Design and Cell Mimicry' in Aarhus, Denmark. The lock-down events of 2020 put to practice worldwide to prevent the spread of the SARS-CoV-2 has led us to postpone the conference to a later date (not set at the time of publication of this editorial). We are committed to hold the conference as soon as the epidemiological situation permits, and we hope that this Special Issue will spur the interest of the broad scientific community in the field of artificial biology. As organizers of this conference and guest editors of this Special Issue, we thank all those who supported the conference as keynote and invited speakers as well as all the authors of the articles that comprise this issue.