Contact interactions between epitheliocytes and fibroblasts: Formation of heterotypic cadherin-containing adhesion sites is accompanied by local cytoskeletal reorganization

Abstract

Contact interactions between different cell types play a number of important roles in development, for example in cell sorting, tissue organization, and ordered migration of cells. The nature of such heterocellular interactions, in contrast to interactions between cells of the same type, remains largely unknown. In this report, we present experimental data examining the dynamics of heterocellular interactions between epitheliocytes and fibroblasts, which express different cadherin cell adhesion molecules and possess different actin cytoskeletal organizations. Our analysis revealed two striking features of heterocellular contact. First, the active free edge of an epitheliocyte reorganizes its actin cytoskeleton after making contact with a fibroblast. Upon contact with the leading edge of a fibroblast, epitheliocytes disassemble their marginal bundle of actin filaments and reassemble actin filaments into a geometric organization more typical of a fibroblast lamella. Second, epitheliocytes and fibroblasts form cell-cell adhesion structures that have an irregular organization and are associated with components of cell adhesion complexes. The structural organization of these adhesions is more closely related to the type of contacts formed between fibroblasts rather than to those between epitheliocytes. Heterotypic epithelio-fibroblastic contacts, like homotypic contacts between fibroblasts, are transient and do not lead to formation of stable contact interactions. We suggest that heterocellular contact interactions in culture may be regarded as models of how tissue systems consisting of epithelia and mesenchyme interact and become organized in vivo.

Rho overexpression leads to mitosis-associated detachment of cells from epithelial sheets: A link to the mechanism of cancer dissemination

“…2A) and sheets that contain circumferential bundles of actin filaments associated with Ecadherin-containing cell-cell contacts (18). In monolayers, individual cells have actin bundles and stress fibers with paxillin-positive focal contacts at their ends as well as networks of microtubules (3).…”

Quantification of the forces driving self-assembly of three-dimensional microtissues

“…When loading was decreased by lowering the slope of the peg, H35 toroids traveled farther up the peg, indicating that the weight of the microtissue is a limiting factor in its power output. Another possible explanation could be that NHFs have a radially arranged cytoskeletal network (3), whereas H35s, as an epithelial cell, have a cortically arranged cytoskeletal network (23). A radial cytoskeletal network may be more efficient at exerting power than a cortical cytoskeleton, and so an even higher dose of Y-27632 may be necessary to fully block Fig.…”

Distinct biological events generated by ECM proteolysis by two homologous collagenases

“…We examined the effect of this ECM on rat-1 fibroblasts, which are known to be sensitive to ECM composition and rigidity. Moreover, these cells, much like epithelial cells, can exhibit different modes of migration toward different substrates and engage in cell-cell interactions (24,25). Because fibroblasts inherently express ECM proteins and remodeling enzymes, we conducted our experiments at early stages of interaction Significance Extracellular matrix (ECM) proteolysis is an abundant biochemical process.…”