Connexon-mediated cell adhesion drives microtissue self-assembly

Bao B, Jiang J, Yanase T, Nishi Y, Morgan JR.
Source
Department of Molecular Pharmacology, Physiology, and Biotechnology, Center for Biomedical Engineering, Brown University, Providence, RI 02912, USA.

Abstract
Microtissue self-assembly is thought to be driven primarily by cadherins, while connexons have been examined mainly in intercellular coupling. We investigated whether connexon 43 (Cx43)-mediated cell adhesion modulates self-assembly of human KGN granulosa cells, normal human fibroblasts (NHFs), and MCF-7 breast cancer cells seeded into nonadhesive agarose gels. We found that treatment with anti-Cx43 E2 (112 μg/ml), which suppresses Cx43 docking, significantly inhibited the kinetics of KGN and NHF self-assembly compared to the preimmune sera control (41.1 ± 4.5 and 24.5 ± 10.4% at 8 h, respectively). Likewise, gap junction inhibitor carbenoxolone also inhibited self-assembly of KGN, NHF, and MCF-7 cells in a dose-dependent manner that was specific to cell type. In contrast, Gap26 connexin mimetic peptide, which inhibits channel permeability but not docking, accelerated self-assembly of KGN and NHF microtissues. Experiments using selective enzymatic digestion of cell adhesion molecules and neutralizing N-cadherin antibodies further showed that self-assembly was comparably disrupted by inhibiting connexin- and cadherin-mediated adhesion. These findings demonstrate that connexon-mediated cell adhesion and intercellular communication differentially influence microtissue self-assembly, and that their contributions are comparable to those of cadherins.

3D Petri Dishes™ used in this paper (please click catalog numbers for detailed product descriptions):
Catalog #12-60TR and 24-24TR are the MicroTissues Inc products used to measure the rate of self-assembly and rod contraction. Catalog # 12-256, and 24-96 are the MicroTissues, Inc products that grow small spheroids. Catalog # 12-81 and 24-35 are used to grow larger spheroids.

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