Adherens junctions are cellular contact sites that organize epithelial tissues and play well-characterized roles in the coordination of cell collectives. Intercellular contacts are mediated by cadherin- or nectin-based adhesion and intracellularly linked to the actin cytoskeleton via the molecular scaffolds catenin and afadin. In this review, we discuss the mechanisms and roles of these molecular scaffolds for cellular morphogenesis and collective cell behaviour with a focus on neural tissue patterning. We discuss the molecular mechanisms in the conceptual framework of two often opposing, but complementary demands on adherens junctions in developing neural tissues: stability through ‘supracellular’ cytoskeletal linkage across cells versus local, dynamically adhesive cellular interactions in morphogenesis. Molecular scaffolds mediate localization, mechanosensitive adhesion and the regulation of cytoskeleton tension in both mechanistic contexts. These complementary mechanisms allow for collective behaviour that has predominantly been characterized for the patterning of tissues consisting of cell bodies, but was recently shown to also underlie the patterning of an epithelial-like tissue made entirely of neuronal growth cones. Molecular scaffolding of adherens junctions thereby contributes to patterning mechanisms that may apply to diverse tissue types.
Regulation of contraction in striated muscle is controlled by a dual mechanism involving both thin filaments containing actin and thick filaments containing myosin. The thin filament is activated by calcium ions binding to troponin, leading to tropomyosin azimuthal displacement which allows the activation of a regulatory unit (composed of one troponin, one tropomyosin and seven actin monomers) that exposes the actin sites for interaction with the myosin motors. Motor attachment to actin contributes to spreading activation within and beyond a regulatory unit along the thin filament through a cooperative mechanism. We introduce a one-dimensional Ising model to elucidate the mechanism of cooperativity in thin filament activation in relation to the force generated by the attached myosin motor. The model characterizes thin filament activation and cooperativity using only two parameters: one related to calcium concentration and the other to the force exerted by the attached myosin motor, which is modulated by temperature. At any force, the model is able to determine the extent of actin-myosin interactions on a correlation length ranging from two to seven actin monomers in addition to the seven actin monomers of the regulatory unit. Our theoretical predictions are successfully tested on experimental data, and our tests also include the condition of hindered filament activation by the use of the specific drug Omecamtiv Mecarbil (OM). According to our model, the effect of OM results in an anti-cooperativity mechanism accounting for the experimental data.
Regulation of contraction in striated muscle is controlled by a dual mechanism involving both thin filaments containing actin and thick filaments containing myosin. The thin filament is activated by calcium ions binding to troponin, leading to tropomyosin azimuthal displacement which allows the activation of a regulatory unit (composed of one troponin, one tropomyosin and seven actin monomers) that exposes the actin sites for interaction with the myosin motors. Motor attachment to actin contributes to spreading activation within and beyond a regulatory unit along the thin filament through a cooperative mechanism. We introduce a one-dimensional Ising model to elucidate the mechanism of cooperativity in thin filament activation in relation to the force generated by the attached myosin motor. The model characterizes thin filament activation and cooperativity using only two parameters: one related to calcium concentration and the other to the force exerted by the attached myosin motor, which is modulated by temperature. At any force, the model is able to determine the extent of actin-myosin interactions on a correlation length ranging from two to seven actin monomers in addition to the seven actin monomers of the regulatory unit. Our theoretical predictions are successfully tested on experimental data, and our tests also include the condition of hindered filament activation by the use of the specific drug Omecamtiv Mecarbil (OM). According to our model, the effect of OM results in an anti-cooperativity mechanism accounting for the experimental data.
Author summary Phagocytosis is the vital process by which specialised immune cells, such as macrophages, engulf and destroy marked targets such as bacteria, dead cells, or even cancer cells. While this is a cornerstone of our immune defence, the physical forces that govern how a cell stretches its membrane around a target remain difficult to experimentally measure. We developed a new mathematical framework to explore how “membrane tension,” the physical resistance to stretching the cell’s surface, impacts this engulfment. We found that as a cell wraps around a target, rising tension acts like a mechanical brake, slowing the process down or even causing it to stop entirely, a phenomenon known as frustrated phagocytosis. However, our model also shows that cell signalling pathways can overcome this resistance by effectively relaxing the membrane, allowing the cell to complete the job quickly and efficiently. By identifying a specific mechanical window of target sizes that a cell can successfully ingest, our work provides fresh insights into how immune cells interact with their environment. These findings could eventually help scientists design more effective drug delivery systems or better understand underlying biology of how certain pathogens manage to evade the immune system’s reach.
Rxiv cytoskeleton
Rxiv mechanobio