Adherens junctions (AJs) are cell-cell adhesion complexes that are continuously assembled and disassembled, allowing cells within a tissue to respond to forces, biochemical signals and structural changes in their micro environment. Adherens junctions regulate cell shape, maintain tissue integrity and translate actomyosin-generated forces throughout a tissue. A key component of adherens junctions are cadherins. The cadherin protein family are common cell-adhesion molecules (CAMs) that mediate cell-cell contacts at anchoring junctions (e.g. adherens junctions, desmosomes) and at prominent sites of cell-cell communication (e.g. neuronal synapses). There are over 100 different cadherin family members that are grouped into at least 6 subfamilies, including type I classical cadherins, type II atypical cadherins and desmosomal cadherins. Most cadherins adhere by homophilic interactions (i.e. they bind to the same type of cadherin) but certain types (e.g. E-cadherin) also adhere by heterophilic interactions (i.e. they bind other types of cadherin). The interactions can take place laterally on the same cell, called a cis interaction, or between two cells, called a trans interaction. Cadherins also bind the intracellular proteins p120-catenin and β-catenin, after which α-catenin is recruited by β-catenin. A vast network of adhesion receptors, scaffolding proteins, actin regulators and signaling proteins regulate the formation of this complex, via a complex network of interactions, which is currently being characterized and has been named the cadhesome.
Actomyosin refers to the actin-myosin complex that forms within the cytoskeleton. Actomyosin is inherently contractile, with the myosin motor protein able to pull on actin filaments. This property gives rise to contractile fibers that form the basis of skeletal muscle, and even in non-muscle cells, enable cell motility and force generation at the sub-cellular level. During non-muscle actomyosin contractility, non-muscle myosin II uses energy from ATP hydrolysis to slide the actin filament to produce contractile force, and these forces have been implicated in multiple cell functions, such as cell adhesion, establishing cell polarity, and cell migration. During cell division, actomyosin contractility regulates forces on the nucleus which affect DNA synthesis and chromatin organization, and is also required for formation and contraction of the mitotic spindle.
Cells and subcellular structures experience forces from a variety of sources. In general, forces are developed from within the cell via the cytoskeleton (endogenous forces) or come from outside the cell (applied forces). Forces exerted on the cell are often dynamic in nature, requiring the cell to constantly re-evaluate its status and adjust its internal and external morphology accordingly. Although the mechanosensors and mechanotransduction events occur locally at the cell periphery, the forces and biochemical signals are transmitted throughout the cell and are integrated over time. In general, they promote stiffening, softening, and reorientation of cytoskeletal filaments.