Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Abstract

Adherens junctions (AJs) and desmosomes connect the actin and keratin filament networks of adjacent cells into a mechanical unit. Whereas AJs function in mechanosensing and in transducing mechanical forces between the plasma membrane and the actomyosin cytoskeleton, desmosomes and intermediate filaments (IFs) provide mechanical stability required to maintain tissue architecture and integrity when the tissues are exposed to mechanical stress. Desmosomes are essential for stable intercellular cohesion, whereas keratins determine cell mechanics but are not involved in generating tension. Here, we summarize the current knowledge of the role of IFs and desmosomes in tissue mechanics and discuss whether the desmosome-keratin scaffold might be actively involved in mechanosensing and in the conversion of chemical signals into mechanical strength.

Figure 1.

Dispase-based dissociation assay highlights the importance of desmosomes for intercellular cohesion. Only the knockdown of the desmosomal plaque protein plakophilin 1 (PKP1) severely disturbed intercellular cohesion of mouse keratinocytes grown for 24 h in a medium containing 1.2 mM Ca²⁺. The knockdown of the corresponding proteins from adherens junctions (AJs), p120, or p0071/PKP4 did not interfere with mechanical resistance of mouse keratinocytes (A), although the respective protein amounts were considerably decreased as shown by western blot (B).

Figure 2.

The desmosome–keratin complex as a micromechanical scaffold during epidermal differentiation. (A) Expression of keratins K5/14 and interaction with desmosomal protein isoforms forms stable cohesion among cells and protects basal keratinocytes against mechanical stress. Under conditions of tissue homeostasis, stable desmosome–keratin scaffolds prevail. (B) Cells react to wounding (activated keratinocytes) by modulating their micromechanical properties through altering adhesion and the cytoskeleton. Underlying mechanisms involve altered expression of isotype proteins and posttranslational modifications that can diminish adhesion and render cells more migratory. Expression of K6/16/17 coincides with dynamic desmosomes. (C) To withstand increased mechanical stress, for example, in upper strata of the epidermis, number and size of desmosomes are increased and keratin filaments become more abundant, bundled by associated proteins and possibly elevated interkeratin Cys crosslinks. Gray arrow in (C) indicates tissue differentiation. Desmosomes are depicted to indicate stable adhesion (red), to demarcate dynamic, less adhesive (light red), and hyperadhesive complexes (dark red). Keratin filaments are drawn to indicate stable networks (straight blue lines), dynamic, less stable networks (dashed green lines) or to indicate highly resilient, bundled networks (orange thick lines). The above properties result from expression of distinct isotypes, relative abundance, and posttranslational modifications.