Origin of yield stress and mechanical plasticity in biological tissues.

During development and under normal physiological conditions, biological tissues are continuously subjected to substantial mechanical stresses. In response to large deformations cells in a tissue must undergo multicellular rearrangements in order to maintain integrity and robustness. However, how these events are connected in time and space remains unknown.

A shape-driven reentrant jamming transition in confluent monolayers of synthetic cell-mimics.

Many critical biological processes, like wound healing, require densely packed cell monolayers/tissues to transition from a jammed solid-like to a fluid-like state. Although numerical studies anticipate changes in the cell shape alone can lead to unjamming, experimental support for this prediction is not definitive because, in living systems, fluidization due to density changes cannot be ruled out. Additionally, a cell's ability to modulate its motility only compounds difficulties since even in assemblies of rigid active particles, changing the nature of self-propulsion has non-trivial effects on the dynamics.

Cell Division and Motility Enable Hexatic Order in Biological Tissues.

Biological tissues transform between solid- and liquidlike states in many fundamental physiological events. Recent experimental observations further suggest that in two-dimensional epithelial tissues these solid-liquid transformations can happen via intermediate states akin to the intermediate hexatic phases observed in equilibrium two-dimensional melting. The hexatic phase is characterized by quasi-long-range (power-law) orientational order but no translational order, thus endowing some structure to an otherwise structureless fluid.

Regulation of Chromatin Modifications through Coordination of Nucleus Size and Epithelial Cell Morphology Heterogeneity.

Cell morphology heterogeneity within epithelial collectives is a pervasive phenomenon intertwined with tissue mechanical properties. Despite its widespread occurrence, the underlying mechanisms driving cell morphology heterogeneity and its consequential biological ramifications remain elusive. Here, we investigate the dynamic evolution of epithelial cell morphology and nucleus morphology during crowding, unveiling a consistent correlation between the two.

Nuclear size-regulated emergence of topological packing order on growing human lung alveolospheres.

Within multicellular living systems, cells coordinate their positions with spatiotemporal accuracy to form various structures, setting the clock to control developmental processes and trigger maturation. These arrangements can be regulated by tissue topology, biochemical cues, as well as mechanical perturbations. However, the fundamental rules of how local cell packing order is regulated in forming three-dimensional (3D) multicellular architectures remain unclear.

Effect of non-linear strain stiffening in eDAH and unjamming.

In cell clusters, the prominent factors at play encompass contractility-based enhanced tissue surface tension and cell unjamming transition. The former effect pertains to the boundary effect, while the latter constitutes a bulk effect. Both effects share outcomes of inducing significant elongation in cells.

Network physics of attractive colloidal gels: Resilience, rigidity, and phase diagram.

Colloidal gels exhibit solid-like behavior at vanishingly small fractions of solids, owing to ramified space-spanning networks that form due to particle-particle interactions. These networks give the gel its rigidity, and with stronger attractions the elasticity grows as well. The emergence of rigidity can be described through a mean field approach; nonetheless, fundamental understanding of how rigidity varies in gels of different attractions is lacking.

Constitutive model for the rheology of biological tissue.

The rheology of biological tissue is key to processes such as embryo development, wound healing, and cancer metastasis. Vertex models of confluent tissue monolayers have uncovered a spontaneous liquid-solid transition tuned by cell shape; and a shear-induced solidification transition of an initially liquidlike tissue. Alongside this jamming/unjamming behavior, biological tissue also displays an inherent viscoelasticity, with a slow time and rate-dependent mechanics.

Mechanical imbalance between normal and transformed cells drives epithelial homeostasis through cell competition.

Cell competition in epithelial tissue eliminates transformed cells expressing activated oncoproteins to maintain epithelial homeostasis. Although the process is now understood to be of mechanochemical origin, direct mechanical characterization and associated biochemical underpinnings are lacking. Here, we employ tissue-scale stress and compressibility measurements and theoretical modeling to unveil a mechanical imbalance between normal and transformed cells, which drives cell competition.

Nature-inspired designs for disordered acoustic bandgap materials.

We introduce an amorphous mechanical metamaterial inspired by how cells pack in biological tissues. The spatial heterogeneity in the local stiffness of these materials has been recently shown to impact the mechanics of confluent biological tissues and cancer tumor invasion. Here we use this bio-inspired structure as a design template to construct mechanical metamaterials and show that this heterogeneity can give rise to amorphous cellular solids with large, tunable acoustic bandgaps.

Discontinuous rigidity transition associated with shear jamming in granular simulations.

We investigate the rigidity transition associated with shear jamming in frictionless, as well as frictional, disk packings in the quasi-static regime and at low shear rates. For frictionless disks, the transition under quasi-static shear is discontinuous, with an instantaneous emergence of a system spanning rigid clusters at the jamming transition. For frictional systems, the transition appears continuous for finite shear rates, but becomes sharper for lower shear rates.

Bridging the gap between collective motility and epithelial-mesenchymal transitions through the active finite voronoi model.

We introduce an active version of the recently proposed finite Voronoi model of epithelial tissue. The resultant Active Finite Voronoi (AFV) model enables the study of both confluent and non-confluent geometries and transitions between them, in the presence of active cells. Our study identifies six distinct phases, characterized by aggregation-segregation, dynamical jamming-unjamming, and epithelial-mesenchymal transitions (EMT), thereby extending the behavior beyond that observed in previously studied vertex-based models.

Matrix confinement modulates 3D spheroid sorting and burst-like collective migration.

While it is known that cells with differential adhesion tend to segregate and preferentially sort, the physical forces governing sorting and invasion in heterogeneous tumors remain poorly understood. To investigate this, we tune matrix confinement, mimicking changes in the stiffness and confinement of the tumor microenvironment, to explore how physical confinement influences individual and collective cell migration in 3D spheroids. High levels of confinement lead to cell sorting while reducing matrix confinement triggers the collective fluidization of cell motion.

Epithelial layer fluidization by curvature-induced unjamming.

The transition of an epithelial layer from a stationary, quiescent state to a highly migratory, dynamic state is required for wound healing, development, and regeneration. This transition, known as the unjamming transition (UJT), is responsible for epithelial fluidization and collective migration. Previous theoretical models have primarily focused on the UJT in flat epithelial layers, neglecting the effects of strong surface curvature characteristic of the epithelium in vivo.

Compressive stress drives adhesion-dependent unjamming transitions in breast cancer cell migration.

Cellular unjamming is the collective fluidization of cell motion and has been linked to many biological processes, including development, wound repair, and tumor growth. In tumor growth, the uncontrolled proliferation of cancer cells in a confined space generates mechanical compressive stress. However, because multiple cellular and molecular mechanisms may be operating simultaneously, the role of compressive stress in unjamming transitions during cancer progression remains unknown.

Shear-Driven Solidification and Nonlinear Elasticity in Epithelial Tissues.

Biological processes, from morphogenesis to tumor invasion, spontaneously generate shear stresses inside living tissue. The mechanisms that govern the transmission of mechanical forces in epithelia and the collective response of the tissue to bulk shear deformations remain, however, poorly understood. Using a minimal cell-based computational model, we investigate the constitutive relation of confluent tissues under simple shear deformation.

Configurational fingerprints of multicellular living systems.

Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder.

Weighting of toilet assessment scheme in China implementing analytic hierarchy process.

Advancing toilet technologies to address public health and sanitation issues are a concern of governments and organizations. This article mainly studies the assessment methods for the public toilets and some rural toilets considering from design to demolition to assist for the innovation of toilet technologies. The Analytic Hierarchy Process (AHP) and Life Cycle Assessment (LCA) methods were adopted to identify the assessment indicators and rank the weight.

LRRC75A-AS1 targets miR-199b-5p/PDCD4 axis to repress multiple myeloma.

Background: Multiple functions of miR-199b-5p in diseases have been demonstrated by existing studies. However, never has the correlation between miR-199b-5p and multiple myeloma (MM) been established.

Methods: qRT-PCR analyzed RNA expression and western blot measured protein expression.

In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition.

The epithelial-to-mesenchymal transition (EMT) and the unjamming transition (UJT) each comprises a gateway to cellular migration, plasticity and remodeling, but the extent to which these core programs are distinct, overlapping, or identical has remained undefined. Here, we triggered partial EMT (pEMT) or UJT in differentiated primary human bronchial epithelial cells. After triggering UJT, cell-cell junctions, apico-basal polarity, and barrier function remain intact, cells elongate and align into cooperative migratory packs, and mesenchymal markers of EMT remain unapparent.