Membrane and acto-myosin tension promote clustering of adhesion proteins

Abstract

Physicists have studied the aggregation of adhesive proteins, giving a central role to the elastic properties of membranes, whereas cell biologists have put the emphasis on the cytoskeleton. However, there is a dramatic lack of experimental studies probing both contributions on cellular systems. Here, we tested both mechanisms on living cells. We compared, for the same cell line, the growth of cadherin-GFP patterns on recombinant cadherin-coated surfaces, with the growth of vinculin-GFP patterns on extracellular matrix protein-coated surfaces by using evanescent wave microscopy. In our setup, cadherins are not linked to actin, whereas vinculins are. This property allows us to compare formation of clusters with proteins linked or not to the cytoskeleton and thus study the role of membrane versus cytoskeleton in protein aggregation. Strikingly, the motifs we obtained on both surfaces share common features: they are both elongated and located at the cell edges. We showed that a local force application can impose this symmetry breaking in both cases. However, the origin of the force is different as demonstrated by drug treatment (butanedione monoxime) and hypotonic swelling. Cadherins aggregate when membrane tension is increased, whereas vinculins (cytoplasmic proteins of focal contacts) aggregate when acto-myosin stress fibers are pulling. We propose a mechanism by which membrane tension is localized at cell edges, imposing flattening of membrane and enabling aggregation of cadherins by diffusion. In contrast, cytoplasmic proteins of focal contacts aggregate by opening cryptic sites in focal contacts under acto-myosin contractility.

Myosin 1g regulates cytoskeleton plasticity, cell migration, exocytosis, and endocytosis in B lymphocytes

“…It has been described that perturbation of cytoskeleton integrity and membrane tension immediately arrest cells in their regular spherical shape, thus abolishing spreading on the substrate [44]. Additionally, it has been observed in endothelial cell lines that the increase in membrane tension stimulate adhesion molecules aggregation favoring adhesive contacts between the cell surface and the substrate by bringing together both as a tension-induced membrane flattening occurs [45]. Accordingly, a decreased membrane tension in B cells due to Myo1g absence could be because of a misregulation in this adhesive process.…”

Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ

“…It is known that membrane tension directly influences the extrusion force of tethers from the cell membrane (Hochmuth and Evans, 1982); therefore, reduction in tether forces suggests that membrane tension might be affected in DFCs. As membrane tension has been proposed to regulate the mobility of membrane proteins and hence their clustering at the plasma membrane (Delanoe-Ayari et al, 2004;Oghalai et al, 2000), it is possible that tension might play a role in the reduced cell-cell adhesion properties of PCP-impaired DFCs. Further analyses will be needed to clarify this possibility.…”

Vesicles surfing on a lipid bilayer: Self-induced haptotactic motion

“…At the level of the cell membrane, cell-cell or cell-extracellular matrix adhesion is mediated by specific ligand-receptor pairs, such as cadherincadherin or integrin-fibronectin (1). Many efforts have been devoted to decipher cell adhesion on different types of substrates (2)(3)(4)(5)(6) and to analyze the intracellular signaling pathway leading to the formation of complex adhesion structures (7,8). In parallel, physicists have used simple model systems without cytoskeleton to understand the static and dynamic behavior of membranes adhering on solid substrates.…”