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  1. Article ; Online: Viscoelastic properties of epithelial cells.

    Janshoff, Andreas

    Biochemical Society transactions

    2022  Volume 49, Issue 6, Page(s) 2687–2695

    Abstract: Epithelial cells form tight barriers that line both the outer and inner surfaces of organs and cavities and therefore face diverse environmental challenges. The response to these challenges relies on the cells' dynamic viscoelastic properties, playing a ... ...

    Abstract Epithelial cells form tight barriers that line both the outer and inner surfaces of organs and cavities and therefore face diverse environmental challenges. The response to these challenges relies on the cells' dynamic viscoelastic properties, playing a pivotal role in many biological processes such as adhesion, growth, differentiation, and motility. Therefore, the cells usually adapt their viscoelastic properties to mirror the environment that determines their fate and vitality. Albeit not a high-throughput method, atomic force microscopy is still among the dominating methods to study the mechanical properties of adherent cells since it offers a broad range of forces from Piconewtons to Micronewtons at biologically significant time scales. Here, some recent work of deformation studies on epithelial cells is reviewed with a focus on viscoelastic models suitable to describe force cycle measurements congruent with the architecture of the actin cytoskeleton. The prominent role of the cortex in the cell's response to external forces is discussed also in the context of isolated cortex extracts on porous surfaces.
    MeSH term(s) Elasticity ; Epithelial Cells/cytology ; Humans ; Microscopy, Atomic Force ; Viscosity
    Language English
    Publishing date 2022-03-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 184237-7
    ISSN 1470-8752 ; 0300-5127
    ISSN (online) 1470-8752
    ISSN 0300-5127
    DOI 10.1042/BST20210476
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Viscoelasticity of basal plasma membranes and cortices derived from MDCK II cells.

    Janshoff, Andreas

    Biophysical reports

    2021  Volume 1, Issue 2, Page(s) 100024

    Abstract: The mechanical properties of cells are largely determined by the architecture and dynamics of their viscoelastic cortex, which consists of a contractile, cross-linked actin mesh attached to the plasma membrane via linker proteins. Measuring the ... ...

    Abstract The mechanical properties of cells are largely determined by the architecture and dynamics of their viscoelastic cortex, which consists of a contractile, cross-linked actin mesh attached to the plasma membrane via linker proteins. Measuring the mechanical properties of adherent, polarized epithelial cells is usually limited to the upper, i.e., apical side, of the cells because of their accessibility on culture dishes. Therefore, less is known about the viscoelastic properties of basal membranes. Here, I investigate the viscoelastic properties of basolateral membranes derived from polarized MDCK II epithelia in response to external deformation and compare them to living cells probed at the apical side. MDCK II cells were grown on porous surfaces to confluence, and the upper cell body was removed via a squirting-lysis protocol. The free-standing, defoliated basal membranes were subject to force indentation and relaxation experiments permitting a precise assessment of cortical viscoelasticity. A new theoretical framework to describe the force cycles is developed and applied to obtain the time-dependent area compressibility modulus of cell cortices from adherent cells. Compared with the viscoelastic response of living cells, the basolateral membranes are substantially less fluid and stiffer but obey to the same universal scaling law if excess area is taken correctly into account.
    Language English
    Publishing date 2021-09-14
    Publishing country United States
    Document type Journal Article
    ISSN 2667-0747
    ISSN (online) 2667-0747
    DOI 10.1016/j.bpr.2021.100024
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  3. Article ; Online: Author Correction: Cytosolic actin isoforms form networks with different rheological properties that indicate specific biological function.

    Nietmann, Peter / Kaub, Kevin / Suchenko, Andrejus / Stenz, Susanne / Warnecke, Claas / Balasubramanian, Mohan K / Janshoff, Andreas

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1242

    Language English
    Publishing date 2024-02-09
    Publishing country England
    Document type Published Erratum
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45715-z
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  4. Article ; Online: Integrated machine learning and multimodal data fusion for patho-phenotypic feature recognition in iPSC models of dilated cardiomyopathy.

    Wali, Ruheen / Xu, Hang / Cheruiyot, Cleophas / Saleem, Hafiza Nosheen / Janshoff, Andreas / Habeck, Michael / Ebert, Antje

    Biological chemistry

    2024  

    Abstract: Integration of multiple data sources presents a challenge for accurate prediction of molecular patho-phenotypic features in automated analysis of data from human model systems. Here, we applied a machine learning-based data integration to distinguish ... ...

    Abstract Integration of multiple data sources presents a challenge for accurate prediction of molecular patho-phenotypic features in automated analysis of data from human model systems. Here, we applied a machine learning-based data integration to distinguish patho-phenotypic features at the subcellular level for dilated cardiomyopathy (DCM). We employed a human induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) model of a DCM mutation in the sarcomere protein troponin T (TnT), TnT-R141W, compared to isogenic healthy (WT) control iPSC-CMs. We established a multimodal data fusion (MDF)-based analysis to integrate source datasets for Ca
    Language English
    Publishing date 2024-04-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1334659-3
    ISSN 1437-4315 ; 1431-6730 ; 1432-0355
    ISSN (online) 1437-4315
    ISSN 1431-6730 ; 1432-0355
    DOI 10.1515/hsz-2024-0023
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  5. Article ; Online: Detachment of giant liposomes - coupling of receptor mobility and membrane shape.

    Witt, Hannes / Vache, Marian / Cordes, Andrea / Janshoff, Andreas

    Soft matter

    2020  Volume 16, Issue 27, Page(s) 6424–6433

    Abstract: Cellular adhesion is an intricate physical process controlled by ligand-receptor affinity, density, mobility, and external forces transmitted through the elastic properties of the cell. As a model for cellular adhesion we study the detachment of cell- ... ...

    Abstract Cellular adhesion is an intricate physical process controlled by ligand-receptor affinity, density, mobility, and external forces transmitted through the elastic properties of the cell. As a model for cellular adhesion we study the detachment of cell-sized liposomes and membrane-coated silica beads from supported bilayers using atomic force microscopy. Adhesion between the two surfaces is mediated by the interaction between the adhesive lipid anchored saccharides lactosylceramide and the ganglioside G
    MeSH term(s) Cell Adhesion ; Ligands ; Liposomes ; Membranes ; Microscopy, Atomic Force
    Chemical Substances Ligands ; Liposomes
    Language English
    Publishing date 2020-06-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2191476-X
    ISSN 1744-6848 ; 1744-683X
    ISSN (online) 1744-6848
    ISSN 1744-683X
    DOI 10.1039/d0sm00863j
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  6. Article ; Online: Using Force Spectroscopy to Probe Coiled-Coil Assembly and Membrane Fusion.

    Witt, Hannes / Janshoff, Andreas

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1860, Page(s) 145–159

    Abstract: Force spectroscopy allows the manipulation of single molecules and the characterization of their properties and interactions thereby rendering it a powerful tool for biological sciences. Force spectroscopy at the level of individual molecules requires ... ...

    Abstract Force spectroscopy allows the manipulation of single molecules and the characterization of their properties and interactions thereby rendering it a powerful tool for biological sciences. Force spectroscopy at the level of individual molecules requires force resolution in the piconewton regime as achieved by optical tweezers (OT), magnetic tweezers (MT), and atomic force microscopy (AFM) with AFM providing the largest force range from tenth of piconewton to several micronewton. In membrane probe spectroscopy the commonly used sharp cantilever tip is replaced by a lipid-coated glass sphere. This technique expands the scope of force spectroscopy to processes at and between lipid bilayers, like the formation of coiled coils between SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) proteins as well as subsequent membrane fusion. To this end, two solid-supported membranes equipped with SNARE proteins or fusion peptides are separately deposited on a flat glassy surface and on a micrometer glass sphere attached to the end of a tipless AFM cantilever. These two membranes are rapidly brought into contact until a defined force is reached. The AFM deflection readout is used to monitor the distance between the two bilayers, which allows to observe and identify fusion processes of the two lipid membranes, while the forces needed to separate the two surfaces give insights into the formation of SNARE complexes. By changing the contact pressure one can access fusion kinetics and to some extent reconstruct the energy landscape of membrane fusion. In this chapter we describe the preparation of membrane-coated colloidal probes attached to AFM cantilevers, experimental procedures, and necessary data analysis to perform membrane probe spectroscopy in the presence of fusogenic peptides or proteins.
    MeSH term(s) Lipid Bilayers/chemistry ; Lipid Bilayers/metabolism ; Membrane Fusion ; Membrane Lipids/chemistry ; Membrane Lipids/metabolism ; Microscopy, Atomic Force/instrumentation ; Microscopy, Atomic Force/methods ; Optical Tweezers ; Protein Domains ; Proteolipids/chemistry ; Proteolipids/metabolism ; SNARE Proteins/chemistry ; SNARE Proteins/metabolism ; Spectrum Analysis/instrumentation ; Spectrum Analysis/methods
    Chemical Substances Lipid Bilayers ; Membrane Lipids ; Proteolipids ; SNARE Proteins ; proteoliposomes
    Language English
    Publishing date 2018-10-10
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-8760-3_8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Importance of integrity of cell-cell junctions for the mechanics of confluent MDCK II cells.

    Brückner, Bastian Rouven / Janshoff, Andreas

    Scientific reports

    2018  Volume 8, Issue 1, Page(s) 14117

    Abstract: Intercellular junctions are important mechanical couplers between cells in epithelial layers providing adhesion and intercellular communication. Regulation of the junctions occurs in cellular processes such as layer formation, epithelial-to-mesenchymal ... ...

    Abstract Intercellular junctions are important mechanical couplers between cells in epithelial layers providing adhesion and intercellular communication. Regulation of the junctions occurs in cellular processes such as layer formation, epithelial-to-mesenchymal transition, embryogenesis, and cancer progression. Many studies addressed the role of force generation in cells for establishing lateral cell-cell junctions and the role of cellular force transmission in tissue formation and maintenance. Our atomic force microscopy- (AFM) based study shed light on the role of both, tight junctions and adherens junctions for the mechanical properties of individual epithelial cells that are part of a confluent monolayer. We found that tight junctions are important for the establishment of a functional barrier-forming layer but impairing them does not reduce the mechanical integrity of cells. Depletion of ZO-1 results in a weak increase in cortical tension. An opposite effect was observed for disruption of E-cadherin-mediated adherens junctions using DTT. Opening of adherens junctions leads to substantial alterations of cellular mechanics such as reduced overall stiffness, but these changes turned out to be reversible after re-establishing disulfide bridges in E-cadherin by removal of DTT. We found that regulatory mechanisms exist that preserve mechanical integrity during recovery of disrupted adherens junctions.
    MeSH term(s) Adherens Junctions/metabolism ; Animals ; Cadherins/metabolism ; Cell Adhesion/physiology ; Dogs ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Intercellular Junctions/physiology ; Madin Darby Canine Kidney Cells ; Microscopy, Atomic Force ; Tight Junctions/metabolism ; Zonula Occludens-1 Protein/metabolism
    Chemical Substances Cadherins ; Zonula Occludens-1 Protein
    Language English
    Publishing date 2018-09-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-32421-2
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  8. Article ; Online: Special issue: Multicomponent lipid membranes-how molecular organisation leads to function.

    de Groot, Bert / Janshoff, Andreas / Steinem, Claudia / Zweckstetter, Markus

    European biophysics journal : EBJ

    2021  Volume 50, Issue 2, Page(s) 107–108

    MeSH term(s) Lipid Bilayers ; Membrane Lipids
    Chemical Substances Lipid Bilayers ; Membrane Lipids
    Language English
    Publishing date 2021-04-15
    Publishing country Germany
    Document type Editorial
    ZDB-ID 283671-3
    ISSN 1432-1017 ; 0175-7571
    ISSN (online) 1432-1017
    ISSN 0175-7571
    DOI 10.1007/s00249-021-01535-3
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  9. Article ; Online: Cytosolic actin isoforms form networks with different rheological properties that indicate specific biological function.

    Nietmann, Peter / Kaub, Kevin / Suchenko, Andrejus / Stenz, Susanne / Warnecke, Claas / Balasubramanian, Mohan K / Janshoff, Andreas

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 7989

    Abstract: The implications of the existence of different actins expressed in epithelial cells for network mechanics and dynamics is investigated by microrheology and confocal imaging. γ-actin predominately found in the apical cortex forms stiffer networks compared ...

    Abstract The implications of the existence of different actins expressed in epithelial cells for network mechanics and dynamics is investigated by microrheology and confocal imaging. γ-actin predominately found in the apical cortex forms stiffer networks compared to β-actin, which is preferentially organized in stress fibers. We attribute this to selective interactions with Mg
    MeSH term(s) Actins/metabolism ; Actinin/metabolism ; Myosins/metabolism ; Protein Isoforms ; Ions ; Actin Cytoskeleton/metabolism
    Chemical Substances Actins ; Actinin (11003-00-2) ; Myosins (EC 3.6.4.1) ; Protein Isoforms ; Ions
    Language English
    Publishing date 2023-12-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-43653-w
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  10. Article ; Online: HAV-Peptides Attached to Colloidal Probes Faithfully Detect E-Cadherins Displayed on Living Cells.

    Toy, Silan / Dietz, Jörn / Naumann, Peter / Trothe, Janina / Thomas, Franziska / Diederichsen, Ulf / Steinem, Claudia / Janshoff, Andreas

    Chemistry (Weinheim an der Bergstrasse, Germany)

    2023  Volume 29, Issue 39, Page(s) e202203904

    Abstract: Cell adhesion molecules are crucial for a variety of biological processes, including wound healing, barrier formation and tissue homeostasis. One of them is E-cadherin which is generally found at adherent junctions between epithelial cells. To identify ... ...

    Abstract Cell adhesion molecules are crucial for a variety of biological processes, including wound healing, barrier formation and tissue homeostasis. One of them is E-cadherin which is generally found at adherent junctions between epithelial cells. To identify this molecule on the surface of cells, E-cadherin mimetic peptides with a critical amino acid sequence of HAV (histidine-alanine-valine) were synthesized and attached to solid-supported membranes covering colloidal probes. Two different functionalization strategies were established, one based on the complexation of DOGS-NTA(Ni) with a polyhistidine-tagged HAV-peptide and the other one relying on the formation of a HAV-lipopeptide using in situ maleimide-thiol coupling. Binding studies were performed to verify the ability of the peptides to attach to the membrane surface. Compared to the non-covalent attachment via the His-tag, we achieved a higher yield by lipopeptide formation. Colloidal probes functionalized with HAV-peptides were employed to measure the presence of E-cadherins on living cells either using video particle tracking or force spectroscopy. Here, human HaCaT cells were examined confirming the specific interaction of the HAV-peptide with the E-cadherin of the cells. Statistical methods were also used to determine the number of single-bond ruptures and the force of a single bond. These findings may be essential for the development of novel biosynthetic materials given their potential to become increasingly relevant in medical applications.
    MeSH term(s) Humans ; Cadherins/chemistry ; Cadherins/metabolism ; Cell Line ; Amino Acid Sequence ; Epithelial Cells ; Lipopeptides/metabolism
    Chemical Substances Cadherins ; Lipopeptides
    Language English
    Publishing date 2023-05-31
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1478547-X
    ISSN 1521-3765 ; 0947-6539
    ISSN (online) 1521-3765
    ISSN 0947-6539
    DOI 10.1002/chem.202203904
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