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  1. Article: "Essentially, all models are wrong, but some are useful"-a cross-disciplinary agenda for building useful models in cell biology and biophysics.

    Berro, Julien

    Biophysical reviews

    2018  Volume 10, Issue 6, Page(s) 1637–1647

    Abstract: Intuition alone often fails to decipher the mechanisms underlying the experimental data in Cell Biology and Biophysics, and mathematical modeling has become a critical tool in these fields. However, mathematical modeling is not as widespread as it could ... ...

    Abstract Intuition alone often fails to decipher the mechanisms underlying the experimental data in Cell Biology and Biophysics, and mathematical modeling has become a critical tool in these fields. However, mathematical modeling is not as widespread as it could be, because experimentalists and modelers often have difficulties communicating with each other, and are not always on the same page about what a model can or should achieve. Here, we present a framework to develop models that increase the understanding of the mechanisms underlying one's favorite biological system. Development of the most insightful models starts with identifying a good biological question in light of what is known and unknown in the field, and determining the proper level of details that are sufficient to address this question. The model should aim not only to explain already available data, but also to make predictions that can be experimentally tested. We hope that both experimentalists and modelers who are driven by mechanistic questions will find these guidelines useful to develop models with maximum impact in their field.
    Language English
    Publishing date 2018-11-12
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 2486483-3
    ISSN 1867-2469 ; 1867-2450
    ISSN (online) 1867-2469
    ISSN 1867-2450
    DOI 10.1007/s12551-018-0478-4
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  2. Article ; Online: Isolated THATCH domain of End4 is unable to bind F-actin independently in the fission yeast

    Ren, Yuan / Berro, Julien

    microPublication biology

    2022  Volume 2022

    Abstract: Clathrin mediated endocytosis (CME) in the fission ... ...

    Abstract Clathrin mediated endocytosis (CME) in the fission yeast
    Language English
    Publishing date 2022-01-06
    Publishing country United States
    Document type Journal Article
    ISSN 2578-9430
    ISSN (online) 2578-9430
    DOI 10.17912/micropub.biology.000508
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: 2A peptide from ERBV-1 efficiently separates endogenous protein domains in the fission yeast

    Ren, Yuan / Lin, Qun / Berro, Julien

    microPublication biology

    2023  Volume 2023

    Abstract: 2A peptides are widely used for polycistronic gene expression from vectors. In contrast, the separation of endogenous genes via 2A peptides has been largely unexplored. We show that in fission ... ...

    Abstract 2A peptides are widely used for polycistronic gene expression from vectors. In contrast, the separation of endogenous genes via 2A peptides has been largely unexplored. We show that in fission yeast
    Language English
    Publishing date 2023-09-11
    Publishing country United States
    Document type Journal Article
    ISSN 2578-9430
    ISSN (online) 2578-9430
    DOI 10.17912/micropub.biology.000941
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Endocytosis against high turgor pressure is made easier by partial coating and freely rotating base.

    Ma, Rui / Berro, Julien

    Biophysical journal

    2021  Volume 120, Issue 9, Page(s) 1625–1640

    Abstract: During clathrin-mediated endocytosis, a patch of flat plasma membrane is deformed into a vesicle. In walled cells, such as plants and fungi, the turgor pressure is high and pushes the membrane against the cell wall, thus hindering membrane ... ...

    Abstract During clathrin-mediated endocytosis, a patch of flat plasma membrane is deformed into a vesicle. In walled cells, such as plants and fungi, the turgor pressure is high and pushes the membrane against the cell wall, thus hindering membrane internalization. In this work, we study how a patch of membrane is deformed against turgor pressure by force and by curvature-generating proteins. We show that a large amount of force is needed to merely start deforming the membrane and an even larger force is needed to pull a membrane tube. The magnitude of these forces strongly depends on how the base of the membrane is constrained and how the membrane is coated with curvature-generating proteins. In particular, these forces can be reduced by partially, but not fully, coating the membrane patch with curvature-generating proteins. Our theoretical results show excellent agreement with experimental data.
    MeSH term(s) Actins ; Cell Membrane ; Cell Wall ; Clathrin ; Endocytosis
    Chemical Substances Actins ; Clathrin
    Language English
    Publishing date 2021-03-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2021.02.033
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  5. Article ; Online: Rapid adaptation of endocytosis, exocytosis, and eisosomes after an acute increase in membrane tension in yeast cells.

    Lemière, Joël / Ren, Yuan / Berro, Julien

    eLife

    2021  Volume 10

    Abstract: During clathrin-mediated endocytosis (CME) in eukaryotes, actin assembly is required to overcome large membrane tension and turgor pressure. However, the molecular mechanisms by which the actin machinery adapts to varying membrane tension remain unknown. ...

    Abstract During clathrin-mediated endocytosis (CME) in eukaryotes, actin assembly is required to overcome large membrane tension and turgor pressure. However, the molecular mechanisms by which the actin machinery adapts to varying membrane tension remain unknown. In addition, how cells reduce their membrane tension when they are challenged by hypotonic shocks remains unclear. We used quantitative microscopy to demonstrate that cells rapidly reduce their membrane tension using three parallel mechanisms. In addition to using their cell wall for mechanical protection, yeast cells disassemble eisosomes to buffer moderate changes in membrane tension on a minute time scale. Meanwhile, a temporary reduction in the rate of endocytosis for 2-6 min and an increase in the rate of exocytosis for at least 5 min allow cells to add large pools of membrane to the plasma membrane. We built on these results to submit the cells to abrupt increases in membrane tension and determine that the endocytic actin machinery of fission yeast cells rapidly adapts to perform CME. Our study sheds light on the tight connection between membrane tension regulation, endocytosis, and exocytosis.
    MeSH term(s) Actins/metabolism ; Cell Membrane/metabolism ; Clathrin/metabolism ; Endocytosis/physiology ; Exocytosis ; Saccharomyces cerevisiae/metabolism ; Schizosaccharomyces/metabolism
    Chemical Substances Actins ; Clathrin
    Language English
    Publishing date 2021-05-13
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.62084
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  6. Article ; Online: Force redistribution in clathrin-mediated endocytosis revealed by coiled-coil force sensors.

    Ren, Yuan / Yang, Jie / Fujita, Barbara / Jin, Huaizhou / Zhang, Yongli / Berro, Julien

    Science advances

    2023  Volume 9, Issue 41, Page(s) eadi1535

    Abstract: Forces are central to countless cellular processes, yet in vivo force measurement at the molecular scale remains difficult if not impossible. During clathrin-mediated endocytosis, forces produced by the actin cytoskeleton are transmitted to the plasma ... ...

    Abstract Forces are central to countless cellular processes, yet in vivo force measurement at the molecular scale remains difficult if not impossible. During clathrin-mediated endocytosis, forces produced by the actin cytoskeleton are transmitted to the plasma membrane by a multiprotein coat for membrane deformation. However, the magnitudes of these forces remain unknown. Here, we present new in vivo force sensors that induce protein condensation under force. We measured the forces on the fission yeast Huntingtin-Interacting Protein 1 Related (HIP1R) homolog End4p, a protein that links the membrane to the actin cytoskeleton. End4p is under ~19-piconewton force near the actin cytoskeleton, ~11 piconewtons near the clathrin lattice, and ~9 piconewtons near the plasma membrane. Our results demonstrate that forces are collected and redistributed across the endocytic machinery.
    MeSH term(s) Actins/metabolism ; Protein Binding ; Actin Cytoskeleton/metabolism ; Clathrin/metabolism ; Endocytosis ; Cell Membrane/metabolism
    Chemical Substances Actins ; Clathrin
    Language English
    Publishing date 2023-10-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2810933-8
    ISSN 2375-2548 ; 2375-2548
    ISSN (online) 2375-2548
    ISSN 2375-2548
    DOI 10.1126/sciadv.adi1535
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  7. Article ; Online: Crosslinking actin networks produces compressive force.

    Ma, Rui / Berro, Julien

    Cytoskeleton (Hoboken, N.J.)

    2019  Volume 76, Issue 5, Page(s) 346–354

    Abstract: Actin has been shown to be essential for clathrin-mediated endocytosis in yeast. However, actin polymerization alone is likely insufficient to produce enough force to deform the membrane against the huge turgor pressure of yeast cells. In this paper, we ... ...

    Abstract Actin has been shown to be essential for clathrin-mediated endocytosis in yeast. However, actin polymerization alone is likely insufficient to produce enough force to deform the membrane against the huge turgor pressure of yeast cells. In this paper, we used Brownian dynamics simulations to demonstrate that crosslinking of a meshwork of nonpolymerizing actin filaments is able to produce compressive forces. We show that the force can be up to several thousand pico-Newtons if the crosslinker has a high stiffness. The force decays over time as a result of crosslinker turnover, and is a result of converting chemical binding energy into elastic energy.
    MeSH term(s) Actin Cytoskeleton/chemistry ; Actins/metabolism ; Biomechanical Phenomena ; Compressive Strength ; Cross-Linking Reagents/metabolism ; Elasticity ; Models, Biological ; Torsion, Mechanical
    Chemical Substances Actins ; Cross-Linking Reagents
    Language English
    Publishing date 2019-07-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2534372-5
    ISSN 1949-3592 ; 1949-3584
    ISSN (online) 1949-3592
    ISSN 1949-3584
    DOI 10.1002/cm.21552
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  8. Article ; Online: Structural organization and energy storage in crosslinked actin assemblies.

    Ma, Rui / Berro, Julien

    PLoS computational biology

    2018  Volume 14, Issue 5, Page(s) e1006150

    Abstract: During clathrin-mediated endocytosis in yeast cells, short actin filaments (< 200nm) and crosslinking protein fimbrin assemble to drive the internalization of the plasma membrane. However, the organization of the actin meshwork during endocytosis remains ...

    Abstract During clathrin-mediated endocytosis in yeast cells, short actin filaments (< 200nm) and crosslinking protein fimbrin assemble to drive the internalization of the plasma membrane. However, the organization of the actin meshwork during endocytosis remains largely unknown. In addition, only a small fraction of the force necessary to elongate and pinch off vesicles can be accounted for by actin polymerization alone. In this paper, we used mathematical modeling to study the self-organization of rigid actin filaments in the presence of elastic crosslinkers in conditions relevant to endocytosis. We found that actin filaments condense into either a disordered meshwork or an ordered bundle depending on filament length and the mechanical and kinetic properties of the crosslinkers. Our simulations also demonstrated that these nanometer-scale actin structures can store a large amount of elastic energy within the crosslinkers (up to 10kBT per crosslinker). This conversion of binding energy into elastic energy is the consequence of geometric constraints created by the helical pitch of the actin filaments, which results in frustrated configurations of crosslinkers attached to filaments. We propose that this stored elastic energy can be used at a later time in the endocytic process. As a proof of principle, we presented a simple mechanism for sustained torque production by ordered detachment of crosslinkers from a pair of parallel filaments.
    MeSH term(s) Actin Cytoskeleton/chemistry ; Actin Cytoskeleton/metabolism ; Actin Cytoskeleton/ultrastructure ; Cell Membrane/metabolism ; Cell Membrane/ultrastructure ; Computational Biology ; Endocytosis/physiology ; Energy Metabolism/physiology ; Fungal Proteins/chemistry ; Fungal Proteins/metabolism ; Fungal Proteins/ultrastructure ; Kinetics ; Models, Molecular ; Yeasts/cytology
    Chemical Substances Fungal Proteins
    Language English
    Publishing date 2018-05-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1006150
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  9. Article ; Online: A model of actin-driven endocytosis explains differences of endocytic motility in budding and fission yeast.

    Nickaeen, Masoud / Berro, Julien / Pollard, Thomas D / Slepchenko, Boris M

    Molecular biology of the cell

    2021  Volume 33, Issue 3, Page(s) ar16

    Abstract: A comparative study ( ... ...

    Abstract A comparative study (Sun
    MeSH term(s) Actins/metabolism ; Cell Membrane/metabolism ; Endocytosis ; Saccharomyces cerevisiae/metabolism ; Schizosaccharomyces/metabolism
    Chemical Substances Actins
    Language English
    Publishing date 2021-12-15
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E21-07-0362
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  10. Article ; Online: Single-molecule turnover dynamics of actin and membrane coat proteins in clathrin-mediated endocytosis.

    Lacy, Michael M / Baddeley, David / Berro, Julien

    eLife

    2019  Volume 8

    Abstract: Actin dynamics generate forces to deform the membrane and overcome the cell's high turgor pressure during clathrin-mediated endocytosis (CME) in yeast, but precise molecular details are still unresolved. Our previous models predicted that actin filaments ...

    Abstract Actin dynamics generate forces to deform the membrane and overcome the cell's high turgor pressure during clathrin-mediated endocytosis (CME) in yeast, but precise molecular details are still unresolved. Our previous models predicted that actin filaments of the endocytic meshwork continually polymerize and disassemble, turning over multiple times during an endocytic event, similar to other actin systems. We applied single-molecule speckle tracking in live fission yeast to directly measure molecular turnover within CME sites for the first time. In contrast with the overall ~20 s lifetimes of actin and actin-associated proteins in endocytic patches, we detected single-molecule residence times around 1 to 2 s, and similarly high turnover rates of membrane-associated proteins in CME. Furthermore, we find heterogeneous behaviors in many proteins' motions. These results indicate that endocytic proteins turn over up to five times during the formation of an endocytic vesicle, and suggest revising quantitative models of force production.
    MeSH term(s) Actin Cytoskeleton/genetics ; Actin Cytoskeleton/metabolism ; Actins/genetics ; Actins/metabolism ; Capsid Proteins/genetics ; Cell Membrane/genetics ; Clathrin/genetics ; Clathrin/metabolism ; Endocytosis/genetics ; Membrane Proteins/genetics ; Microfilament Proteins/genetics ; Schizosaccharomyces/genetics ; Single Molecule Imaging ; Transport Vesicles/genetics ; Transport Vesicles/metabolism
    Chemical Substances Actins ; Capsid Proteins ; Clathrin ; Membrane Proteins ; Microfilament Proteins
    Language English
    Publishing date 2019-12-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.52355
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