Regulation of intercellular viscosity by E-cadherin-dependent phosphorylation of EGFR in collective cell migration.

Collective cell migration is crucial in various physiological processes, including wound healing, morphogenesis, and cancer metastasis. Adherens Junctions (AJs) play a pivotal role in regulating cell cohesion and migration dynamics during tissue remodeling. While the role and origin of the junctional mechanical tension at AJs have been extensively studied, the influence of the actin cortex structure and dynamics on junction plasticity remains incompletely understood.

Curvature-induced clustering of cell adhesion proteins.

Cell adhesion proteins typically form stable clusters that anchor the cell membrane to its environment. Several works have suggested that cell membrane protein clusters can emerge from a local feedback between the membrane curvature and the density of proteins. Here, we investigate the effect of such a curvature-sensing mechanism in the context of cell adhesion proteins.

Membrane Tilt Drives Phase Separation of Adhesion Receptors.

Cell adhesion receptors are transmembrane proteins that bind cells to their environment. These proteins typically cluster into disk-shaped or linear structures. Here, we show that such clustering patterns spontaneously emerge when the receptor senses the membrane deformation gradient, for example, by reaching a lower-energy conformation when the membrane is tilted relative to the underlying binding substrate.

Interfacial Organization and Forces Arising from Epithelial-Cancerous Monolayer Interactions.

The interfacial interactions between epithelia and cancer cells have profound relevance for tumor development and metastasis. Through monolayer confrontation of MCF10A (nontumorigenic human breast epithelial cells) and MDA-MB-231 (human epithelial breast cancer cells) cells, we investigate the epithelial-cancerous interfacial interactions at the tissue level. We show that the monolayer interaction leads to competitive interfacial morphodynamics and drives an intricate spatial organization of MCF10A cells into multicellular finger-like structures, which further branch into multiple subfinger-like structures.

Two-point optical manipulation reveals mechanosensitive remodeling of cell-cell contacts in vivo.

Biological tissues acquire reproducible shapes during development through dynamic cell behaviors. Most of these behaviors involve the remodeling of cell-cell contacts. During epithelial morphogenesis, contractile actomyosin networks remodel cell-cell contacts by shrinking and extending junctions between lateral cell surfaces.

Structure and Rheology in Vertex Models under Cell-Shape-Dependent Active Stresses.

Biological cells can actively tune their intracellular architecture according to their overall shape. Here we explore the rheological implication of such coupling in a minimal model of a dense cellular material where each cell exerts an active mechanical stress along its axis of elongation. Increasing the active stress amplitude leads to several transitions.

Mechanical stress driven by rigidity sensing governs epithelial stability.

Epithelia act as a barrier against environmental stress and abrasion and they are continuously exposed to environments of various mechanical properties. The impact of this environment on epithelial integrity remains elusive. By culturing epithelial cells on 2D hydrogels, we observe a loss of epithelial monolayer integrity through spontaneous hole formation when grown on soft substrates.

mechanical nociceptors preferentially sense localized poking.

Mechanical nociception is an evolutionarily conserved sensory process required for the survival of living organisms. Previous studies have revealed much about the neural circuits and sensory molecules in mechanical nociception, but the cellular mechanisms adopted by nociceptors in force detection remain elusive. To address this issue, we study the mechanosensation of a fly larval nociceptor (class IV da neurons, c4da) using a customized mechanical device.

Active Nematic Flows over Curved Surfaces.

Cell monolayers are a central model system in the study of tissue biophysics. In vivo, epithelial tissues are curved on the scale of microns, and the curvature's role in the onset of spontaneous tissue flows is still not well understood. Here, we present a hydrodynamic theory for an apical-basal asymmetric active nematic gel on a curved strip.

Spontaneous organization and phase separation of skyrmions in chiral active matter.

Skyrmions are topologically protected vortex-like excitations that hold promise for applications such as information processing and electron manipulation. Here we combine theoretical analysis and numerical simulations to show that skyrmions can spontaneously emerge in chiral active matter without external confinements or regulation. Strikingly, these activity-driven skyrmions can either self-organize into a periodic, stable square lattice consisting of half Néel skyrmions and antiskyrmions, where the in-plane flows display an antiferromagnetic vortex array, or undergo phase separation between skyrmions with different topological numbers.

Implementation of cellular bulk stresses in vertex models of biological tissues.

Vertex models describe biological tissues as tilings of polygons. In standard vertex models, the tissue dynamics result from a balance between isotropic stresses, which are associated with the bulk of the cells, and tensions associated with cell-cell interfaces. However, in this framework it is less obvious how to describe anisotropic stresses arising from the bulk of cells.

Universal Statistical Laws for the Velocities of Collective Migrating Cells.

Migratory dynamics of collective cells is central to the morphogenesis of biological tissues. The statistical distribution of cell velocities in 2D confluent monolayers is measured through large-scale and long-term experiments of various cell types lying on different substrates. A linear relation is discovered between the variability and the mean of cell speeds during the jamming process of confluent cell monolayers, suggesting time-invariant distribution profile of cell velocities.

Pattern Formation and Defect Ordering in Active Chiral Nematics.

Many biological systems display intriguing chiral patterns and dynamics. Here, we present an active nematic theory accounting for individual spin to explore the collective handedness in chiral rod-shaped aggregations. We show that coordinated individual spin and motility can engender a vortex-array pattern with chirality and drive ordering of topological defects.

Collective dynamics of coherent motile cells on curved surfaces.

Cellular dynamic behaviors in organ morphogenesis and embryogenesis are affected by geometrical constraints. In this paper, we investigate how the surface topology and curvature of the underlying substrate tailor collective cell migration. An active vertex model is developed to explore the collective dynamics of coherent cells crawling on curved surfaces.

Dynamic instability and migration modes of collective cells in channels.

Migrating cells constantly experience geometrical confinements in vivo, as exemplified by cancer invasion and embryo development. In this paper, we investigate how intrinsic cellular properties and extrinsic channel confinements jointly regulate the two-dimensional migratory dynamics of collective cells. We find that besides external confinement, active cell motility and cell crowdedness also shape the migration modes of collective cells.

Three-dimensional collective cell motions in an acinus-like lumen.

Collective cell migration is an essential process in embryo development, wound healing, inflammatory response, and cancer invasion. Although cell motions in two-dimensional (2D) monolayers have been studied previously, three-dimensional (3D) collective cell migration, which constantly occurs during embryogenesis such as the establishment of ducts and acini in vivo, remains elusive. In this paper, we develop a cell-based model incorporating cell mechanics and cell motility to address coherent cell motions in a spherical acinus-like lumen with different cell populations.

Dynamic Migration Modes of Collective Cells.

Collective cell migration occurs in a diversity of physiological processes such as wound healing, cancer metastasis, and embryonic morphogenesis. In the collective context, cohesive cells may move as a translational solid, swirl as a fluid, or even rotate like a disk, with scales ranging from several to dozens of cells. In this work, an active vertex model is presented to explore the regulatory roles of social interactions of neighboring cells and environmental confinements in collective cell migration in a confluent monolayer.

A nonlinear poroelastic theory of solid tumors with glycosaminoglycan swelling.

Mechanics plays a crucial role in the growth, development, and therapeutics of tumors. In this paper, a nonlinear poroelastic theory is established to describe the mechanical behaviors of solid tumors. The free-swollen state of a tumor is chosen as the reference state, which enables us to avoid pursuing a dry and stress-free state that is hard to achieve for living tissues.

Activation and synchronization of the oscillatory morphodynamics in multicellular monolayer.

Oscillatory morphodynamics provides necessary mechanical cues for many multicellular processes. Owing to their collective nature, these processes require robustly coordinated dynamics of individual cells, which are often separated too distantly to communicate with each other through biomaterial transportation. Although it is known that the mechanical balance generally plays a significant role in the systems' morphologies, it remains elusive whether and how the mechanical components may contribute to the systems' collective morphodynamics.

Collective dynamics of cancer cells confined in a confluent monolayer of normal cells.

Tumorigenesis often involves specific changes in cell motility and intercellular adhesion. Understanding the collective cancer cell behavior associated with these specific changes could facilitate the detection of malignant characteristics during tumor growth and invasion. In this study, a cellular vertex model is developed to investigate the collective dynamics of a disk-like aggregate of cancer cells confined in a confluent monolayer of normal cells.