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  • Journal ClubJanuary 31, 2022

    3 543 120

    “Cutting and Burning Guts” Nourish the Young

    Caenorhabditis elegans lyse their guts to produce nutritious yolk milk to feed larvae.

    Sun-Kyung Lee

    Mol. Cells 2022; 45(1): 1-3 https://doi.org/10.14348/molcells.2021.5036
  • EditorialJanuary 31, 2022

    0 460 117
  • MinireviewJanuary 31, 2022

    2 987 330
    Abstract

    Abstract : Phase separation is a thermodynamic process leading to the formation of compositionally distinct phases. For the past few years, numerous works have shown that biomolecular phase separation serves as biogenesis mechanisms of diverse intracellular condensates, and aberrant phase transitions are associated with disease states such as neurodegenerative diseases and cancers. Condensates exhibit rich phase behaviors including multiphase internal structuring, noise buffering, and compositional tunability. Recent studies have begun to uncover how a network of intermolecular interactions can give rise to various biophysical features of condensates. Here, we review phase behaviors of biomolecules, particularly with regard to regular solution models of binary and ternary mixtures. We discuss how these theoretical frameworks explain many aspects of the assembly, composition, and miscibility of diverse biomolecular phases, and highlight how a model-based approach can help elucidate the detailed thermodynamic principle for multicomponent intracellular phase separation.

  • MinireviewJanuary 31, 2022

    1 855 260

    Nano-Precision Tweezers for Mechanosensitive Proteins and Beyond

    Taehyun Yang , Celine Park , Sang-Hyun Rah , and Min Ju Shon

    Mol. Cells 2022; 45(1): 16-25 https://doi.org/10.14348/molcells.2022.2026
    Abstract

    Abstract : Mechanical forces play pivotal roles in regulating cell shape, function, and fate. Key players that govern the mechanobiological interplay are the mechanosensitive proteins found on cell membranes and in cytoskeleton. Their unique nanomechanics can be interrogated using single-molecule tweezers, which can apply controlled forces to the proteins and simultaneously measure the ensuing structural changes. Breakthroughs in high-resolution tweezers have enabled the routine monitoring of nanometer-scale, millisecond dynamics as a function of force. Undoubtedly, the advancement of structural biology will be further fueled by integrating static atomic-resolution structures and their dynamic changes and interactions observed with the force application techniques. In this minireview, we will introduce the general principles of single-molecule tweezers and their recent applications to the studies of force-bearing proteins, including the synaptic proteins that need to be categorized as mechanosensitive in a broad sense. We anticipate that the impact of nano-precision approaches in mechanobiology research will continue to grow in the future.

  • MinireviewJanuary 31, 2022

    1 594 208

    Molecular Tension Probes to Quantify Cell-Generated Mechanical Forces

    Kyung Yup Baek , Seohyun Kim , and Hye Ran Koh

    Mol. Cells 2022; 45(1): 26-32 https://doi.org/10.14348/molcells.2022.2049
    Abstract

    Abstract : Living cells generate, sense, and respond to mechanical forces through their interaction with neighboring cells or extracellular matrix, thereby regulating diverse cellular processes such as growth, motility, differentiation, and immune responses. Dysregulation of mechanosensitive signaling pathways is found associated with the development and progression of various diseases such as cancer. Yet, little is known about the mechanisms behind mechano-regulation, largely due to the limited availability of tools to study it at the molecular level. The recent development of molecular tension probes allows measurement of cellular forces exerted by single ligandreceptor interaction, which has helped in revealing the hitherto unknown mechanistic details of various mechanosensitive processes in living cells. Here, we provide an introductory overview of two methods based on molecular tension probes, tension gauge tether (TGT), and molecular tension fluorescence microscopy (MTFM). TGT utilizes the irreversible rupture of double-stranded DNA tether upon application of force in the piconewton (pN) range, whereas MTFM utilizes the reversible extension of molecular springs such as polymer or single-stranded DNA hairpin under applied pN forces. Specifically, the underlying principle of how molecular tension probes measure cell-generated mechanical forces and their applications to mechanosensitive biological processes are described.

  • MinireviewJanuary 31, 2022

    4 1275 481
    Abstract

    Abstract : The various DNA-protein interactions associated with the expression of genetic information involve double-stranded DNA (dsDNA) bending. Due to the importance of the formation of the dsDNA bending structure, dsDNA bending properties have long been investigated in the biophysics field. Conventionally, DNA bendability is characterized by innate averaging data from bulk experiments. The advent of single-molecule methods, such as atomic force microscopy, optical and magnetic tweezers, tethered particle motion, and single-molecule fluorescence resonance energy transfer measurement, has provided valuable tools to investigate not only the static structures but also the dynamic properties of bent dsDNA. Here, we reviewed the single-molecule methods that have been used for investigating dsDNA bendability and new findings related to dsDNA bending. Single-molecule approaches are promising tools for revealing the unknown properties of dsDNA related to its bending, particularly in cells.

  • MinireviewJanuary 31, 2022

    4 839 259
    Abstract

    Abstract : The recently developed correlative super-resolution fluorescence microscopy (SRM) and electron microscopy (EM) is a hybrid technique that simultaneously obtains the spatial locations of specific molecules with SRM and the context of the cellular ultrastructure by EM. Although the combination of SRM and EM remains challenging owing to the incompatibility of samples prepared for these techniques, the increasing research attention on these methods has led to drastic improvements in their performances and resulted in wide applications. Here, we review the development of correlative SRM and EM (sCLEM) with a focus on the correlation of EM with different SRM techniques. We discuss the limitations of the integration of these two microscopy techniques and how these challenges can be addressed to improve the quality of correlative images. Finally, we address possible future improvements and advances in the continued development and wide application of sCLEM approaches.

Mol. Cells
Sep 30, 2022 Vol.45 No.9
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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