Molecular Machines in Cells: Natural, Semi-artificial, and Bioinspired Designs

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Biophysics".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 5675

Special Issue Editor


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Guest Editor
Departments of Neurosurgery and Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
Interests: in situ detection of DNA breaks; FRET DNA molecular probes; DNA damage detection in situ, ex vivo, and in vivo; FRET bio-nanomachines and semi-artificial machines; lymphocyte apoptosis in glioblastomas multiforme
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Special Issue Information

Dear Colleagues,

The 2016 Nobel Prize was awarded for the design and production of molecular machines. This rapidly developing and broad field includes naturally occurring biological machines and the multitude of their fully artificial and semi-artificial analogs.

The focus of this Special Issue of Cells is on the three major groups of molecular machines which use biological mechanisms.

Natural Molecular Machines. Billions of biological molecular machines operate in every living cell. These macromolecular complexes perform critical tasks, such as protein folding, DNA replication, transcription, and transportation of various cargos. Intercellular communication machinery is represented by extracellular vesicles. These metabolic nano-machines transfer nucleic acids and active enzymes between cells. The best studied examples of natural biological machines include ribosomes, plasma membrane pumps, mitotic spindles, and motor proteins: myosin, kinesin, and dynein.

Bio-Inspired Molecular Machines are artificial molecular constructs that apply the mechanisms found in natural molecular machines. These are synthetic artificial machines which adopt the basic principles of biological machines, unique for the micro and nanoscale. Their examples include self-assembling 3D nanostructures and logic gates using the DNA molecule as construction material.

Semi-Artificial Molecular Machines. Due to the complexity of natural biological machines, it is often difficult to decipher their detailed mechanics. To resolve this, a semi-artificial machine design approach was introduced. It produces molecular cyborgs, combining the naturally occurring biomachines with artificial components, which direct their performance toward a new function. These hybrid designs are exemplified by the nanoblinker—the topoisomerase-driven FRET oscillator for DNA damage detection.

This Special Issue is dedicated to natural molecular machines and their artificial and hybrid analogs which employ mechanisms borrowed from nature. We invite contributions about their mechanisms, designs, and applications. Research on the unique biophysical and chemical properties of the normal DNA molecule, which can enable its usage as a building block of molecular machines, is also welcome. Reviews as well as original papers are invited.

Dr. Vladimir V. Didenko
Guest Editor

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Keywords

  • molecular machines in cells
  • biological molecular machines
  • natural molecular machines
  • chromatin spindle molecular machine
  • DNA molecular machine
  • ATPase molecular machine
  • enzymes molecular machines
  • motor proteins
  • semi-biological molecular machine
  • semi-artificial molecular machine
  • semi-synthetic molecular machines
  • fluorescent molecular machine
  • bioinspired molecular machines
  • hybrid molecular machines
  • biomimetic molecular machines
  • molecular motors
  • macromolecular machines
  • bionanomachines
  • artificial molecular machines

Published Papers (4 papers)

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Research

12 pages, 1486 KiB  
Article
Amplification of Signal on Cell Surfaces in Molecular Cascades
by Sergei Rudchenko, Steven Taylor, Nenad Milosavic, Maria Rudchenko, Betina Wedderhoff Tissi, Markus Y. Mapara and Milan N. Stojanovic
Cells 2023, 12(24), 2858; https://doi.org/10.3390/cells12242858 - 18 Dec 2023
Viewed by 853
Abstract
We can formulate mixtures of oligonucleotide–antibody conjugates to act as molecular cascade-based automata that analyze pairs of cell surface markers (CD markers) on individual cells in a manner consistent with the implementation of Boolean logic—for example, by producing a fluorescent label only if [...] Read more.
We can formulate mixtures of oligonucleotide–antibody conjugates to act as molecular cascade-based automata that analyze pairs of cell surface markers (CD markers) on individual cells in a manner consistent with the implementation of Boolean logic—for example, by producing a fluorescent label only if two markers are present. While traditional methods to characterize cells are based on transducing signals from individual cell surface markers, these cascades can be used to combine into a single signal the presence of two or even more CDs. In our original design, oligonucleotide components irreversibly flowed from one antibody to another, driven by increased hybridizations, leading to the magnitude of the final signal on each cell being determined by the surface marker that was the least abundant. This is a significant limitation to the precise labeling of narrow subpopulations, and, in order to overcome it, we changed our design to accomplish signal amplification to a more abundant cell surface marker. We show the AMPLIFY function on two examples: (1) we amplify the fluorescent label from the CD19 marker onto a fivefold more abundant CD45, and (2) we amplify broadly distributed CD45RA to a more constant marker, CD3. We expect this new function to enable the increasingly complex Boolean analysis of cell surfaces. Full article
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12 pages, 3750 KiB  
Article
Spontaneous Confinement of mRNA Molecules at Biomolecular Condensate Boundaries
by Rebecca T. Perelman, Andreas Schmidt, Umar Khan and Nils G. Walter
Cells 2023, 12(18), 2250; https://doi.org/10.3390/cells12182250 - 11 Sep 2023
Viewed by 982
Abstract
Cellular biomolecular condensates, termed ribonucleoprotein (RNP) granules, are often enriched in messenger RNA (mRNA) molecules relative to the surrounding cytoplasm. Yet, the spatial localization and diffusion of mRNAs in close proximity to phase separated RNP granules are not well understood. In this study, [...] Read more.
Cellular biomolecular condensates, termed ribonucleoprotein (RNP) granules, are often enriched in messenger RNA (mRNA) molecules relative to the surrounding cytoplasm. Yet, the spatial localization and diffusion of mRNAs in close proximity to phase separated RNP granules are not well understood. In this study, we performed single-molecule fluorescence imaging experiments of mRNAs in live cells in the presence of two types of RNP granules, stress granules (SGs) and processing bodies (PBs), which are distinct in their molecular composition and function. We developed a photobleaching- and noise-corrected colocalization imaging algorithm that was employed to determine the accurate positions of individual mRNAs relative to the granule’s boundaries. We found that mRNAs are often localized at granule boundaries, an observation consistent with recently published data. We suggest that mRNA molecules become spontaneously confined at the RNP granule boundary similar to the adsorption of polymer molecules at liquid–liquid interfaces, which is observed in various technological and biological processes. We also suggest that this confinement could be due to a combination of intermolecular interactions associated with, first, the screening of a portion of the RNP granule interface by the polymer and, second, electrostatic interactions due to a strong electric field induced by a Donnan potential generated across the thin interface. Full article
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16 pages, 2724 KiB  
Article
The Impact of NAD Bioavailability on DNA Double-Strand Break Repair Capacity in Human Dermal Fibroblasts after Ionizing Radiation
by Maria Svetlova, Ljudmila Solovjeva, Andrey Kropotov and Andrey Nikiforov
Cells 2023, 12(11), 1518; https://doi.org/10.3390/cells12111518 - 31 May 2023
Viewed by 1181
Abstract
Nicotinamide adenine dinucleotide (NAD) serves as a substrate for protein deacetylases sirtuins and poly(ADP-ribose) polymerases, which are involved in the regulation of DNA double-strand break (DSB) repair molecular machinery by various mechanisms. However, the impact of NAD bioavailability on DSB repair remains poorly [...] Read more.
Nicotinamide adenine dinucleotide (NAD) serves as a substrate for protein deacetylases sirtuins and poly(ADP-ribose) polymerases, which are involved in the regulation of DNA double-strand break (DSB) repair molecular machinery by various mechanisms. However, the impact of NAD bioavailability on DSB repair remains poorly characterized. Herein, using immunocytochemical analysis of γH2AX, a marker for DSB, we investigated the effect of the pharmacological modulation of NAD levels on DSB repair capacity in human dermal fibroblasts exposed to moderate doses of ionizing radiation (IR). We demonstrated that NAD boosting with nicotinamide riboside did not affect the efficiency of DSB elimination after the exposure of cells to IR at 1 Gy. Moreover, even after irradiation at 5 Gy, we did not observe any decrease in intracellular NAD content. We also showed that, when the NAD pool was almost completely depleted by inhibition of its biosynthesis from nicotinamide, cells were still able to eliminate IR-induced DSB, though the activation of ATM kinase, its colocalization with γH2AX and DSB repair capacity were reduced in comparison to cells with normal NAD levels. Our results suggest that NAD-dependent processes, such as protein deacetylation and ADP-ribosylation, are important but not indispensable for DSB repair induced by moderate doses of IR. Full article
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24 pages, 4276 KiB  
Article
Extracellular Vesicles Released by Genetically Modified Macrophages Activate Autophagy and Produce Potent Neuroprotection in Mouse Model of Lysosomal Storage Disorder, Batten Disease
by Nazira El-Hage, Matthew J. Haney, Yuling Zhao, Myosotys Rodriguez, Zhanhong Wu, Mori Liu, Carson J. Swain, Hong Yuan and Elena V. Batrakova
Cells 2023, 12(11), 1497; https://doi.org/10.3390/cells12111497 - 29 May 2023
Cited by 2 | Viewed by 1646
Abstract
Over the recent decades, the use of extracellular vesicles (EVs) has attracted considerable attention. Herein, we report the development of a novel EV-based drug delivery system for the transport of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1) to treat Batten disease (BD). Endogenous loading [...] Read more.
Over the recent decades, the use of extracellular vesicles (EVs) has attracted considerable attention. Herein, we report the development of a novel EV-based drug delivery system for the transport of the lysosomal enzyme tripeptidyl peptidase-1 (TPP1) to treat Batten disease (BD). Endogenous loading of macrophage-derived EVs was achieved through transfection of parent cells with TPP1-encoding pDNA. More than 20% ID/g was detected in the brain following a single intrathecal injection of EVs in a mouse model of BD, ceroid lipofuscinosis neuronal type 2 (CLN2) mice. Furthermore, the cumulative effect of EVs repetitive administrations in the brain was demonstrated. TPP1-loaded EVs (EV-TPP1) produced potent therapeutic effects, resulting in efficient elimination of lipofuscin aggregates in lysosomes, decreased inflammation, and improved neuronal survival in CLN2 mice. In terms of mechanism, EV-TPP1 treatments caused significant activation of the autophagy pathway, including altered expression of the autophagy-related proteins LC3 and P62, in the CLN2 mouse brain. We hypothesized that along with TPP1 delivery to the brain, EV-based formulations can enhance host cellular homeostasis, causing degradation of lipofuscin aggregates through the autophagy–lysosomal pathway. Overall, continued research into new and effective therapies for BD is crucial for improving the lives of those affected by this condition. Full article
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