Cis and Trans Cooperativity of E-Cadherin Mediates Adhesion in Biomimetic Lipid Droplets

Lea Laetitia Pontani, Ivane Jorjadze, Jasna Brujic

    Research output: Contribution to journalArticle

    Abstract

    The regulation of cell-cell adhesion is important in cell motility, tissue growth, and for the mechanical integrity of tissues. Although the role of active cytoskeleton dynamics in regulating cadherin interactions is crucial in vivo, here we present a biomimetic emulsion system to characterize the passive E-cadherin-mediated adhesion between droplets. The visualization of a three-dimensional assembly of lipid droplets, functionalized with extracellular E-cadherin domains, reveals a hierarchy of homophilic interactions. First, the high interfacial tension of droplets facilitates trans cadherin-cadherin adhesion, which is strong enough to stabilize looser than random close packing configurations. Second, fluorescence enhancement shows that adding clustering agents, such as calcium or chelating ligands, favor the lateral cis adhesion of the already bound cadherin pairs over the clustering of monomer cadherin on the surface. Finally, above a threshold cadherin and calcium concentration, the cis and trans protein interactions become strong enough to trigger and promote droplet fusion. While E-cadherin is not known to participate in cellular fusion, this mechanism is general because replacing calcium with cholesterol to cluster the cadherin-carrying lipids also promotes fusion. These results suggest that passive clustering, via calcium-induced dimerization or membrane ordering, may contribute to the reinforcement of cell-cell contacts. Alternatively, a molecular switch for fusion offers a route to mixing droplet contents and controlling their size in situ.

    Original languageEnglish (US)
    Pages (from-to)391-399
    Number of pages9
    JournalBiophysical Journal
    Volume110
    Issue number2
    DOIs
    StatePublished - Jan 19 2016

    Fingerprint

    Biomimetics
    Cadherins
    Calcium
    Cluster Analysis
    Lipid Droplets
    Surface Tension
    Dimerization
    Emulsions
    Cytoskeleton
    Cell Adhesion
    Cell Movement
    Fluorescence
    Cholesterol
    Ligands
    Lipids

    ASJC Scopus subject areas

    • Biophysics

    Cite this

    Cis and Trans Cooperativity of E-Cadherin Mediates Adhesion in Biomimetic Lipid Droplets. / Pontani, Lea Laetitia; Jorjadze, Ivane; Brujic, Jasna.

    In: Biophysical Journal, Vol. 110, No. 2, 19.01.2016, p. 391-399.

    Research output: Contribution to journalArticle

    Pontani, Lea Laetitia ; Jorjadze, Ivane ; Brujic, Jasna. / Cis and Trans Cooperativity of E-Cadherin Mediates Adhesion in Biomimetic Lipid Droplets. In: Biophysical Journal. 2016 ; Vol. 110, No. 2. pp. 391-399.
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