Cell-adhesion sensing of the extracellular matrix

The extracellular matrix (ECM) to which cells attach, contains multiple filaments, composed of diverse proteins and glycosaminoglycans.  Collectively, these filament networks act as key systems that direct tissue scaffolding and homeostatic signaling. To clarify the mechanisms underlying the ECM’s specific effects on cells, synthetic matrices with distinct chemical and physical properties are utilized as adhesive substrates. Our studies/findings demonstrate that adhesions mediated via different integrins (e.g., α5β1 vs. αvβ3; see Figure 1) induce the assembly of morphologically distinct focal adhesions.

Figure 1

Adhesions mediated via different integrins induce the assembly of morphologically distinct focal adhesions. The molecular composition of the ECM (here, glass surfaces were coated with fibronectin or vitronectin) and the cellular interaction with these matrices via different integrins (α5β1  and αvβ3, respectively) lead to the formation of focal adhesions with distinct morphology, size and subcellular distribution.

Furthermore, cells can sense diverse physical properties of the ECM, such as the surface rigidity and microtopography, and respond to them, differentially. In studies conducted in collaboration with Joachim Spatz and colleagues at the University of Heidelberg and the Max Planck Institute for Intelligent Systems (Stuttgart, Germany) it was demonstrated that cells also respond to the spacing of adhesion ligands. A spacing of ~50 nm or less is needed to induce focal adhesion formation and assembly (Figure 2).

Figure 2

Signalling by nanopatterned substrates. (a) Scheme of diblock copolymer micelle lithography and biofunctionalization of gold particle substrate (top) in contact with a cell membrane (bottom). A functionalized gold particle with a diameter of ~6 nm on a polyethylene glycol-passivated background is small enough to allow the binding of only a single integrin protein. (b–e) Extended Au nanodot patterns are displayed by SEM. The Au dots form extended, nearly perfect hexagonally close-packed patterns as indicated by the Fourier transform images (inset) which show second order intensity spots. (f-g) Pair of confocal fluorescent micrographs of MC3T3 osteoblasts stained for vinculin (green) and actin (red). The cells interact with Au nanodot patterns with Au dot spacing of 58 nm (f) and 73 nm (g). (h) Projected cell adhesion area per cell adhering to different ligand (dot) separation. (Adapted from Arnold et al., 2004).

Taken together, these studies highlight the capacity of cells to accurately sense the underlying matrix, and respond to it.

Further Reading 
Geblinger, D; Addadi, L; Geiger, B (2010). Nano-topography sensing by osteoclasts.  Journal of Cell Science. 123 (9):1503-1510.
Arnold, M; Hirschfeld-Warneken, VC; Lohmuller, T; Heil, P; Blummel, J; Cavalcanti-Adam, EA; Lopez-Garcia, M; Walther, P; Kessler, H; Geiger, B; Spatz, JP (2008). Induction of cell polarization and migration by a gradient of nanoscale variations in adhesive ligand spacing.  Nano Letters. 8 (7):2063-2069.
Geiger, B; Spatz, JP; Bershadsky, AD (2009). Environmental sensing through focal adhesions.  Nature Reviews Molecular Cell Biology. 10 (1):21-33.