arXiv subjects

Molly McCord

Publications and source records attributed to Molly McCord.

5 recordsLinked to original sources

arXiv2026

Shape-Independent Fluidity in Epithelial Cell Monolayers

Tissue fluidity regulates biological processes such as embryonic development, wound healing, and cancer metastasis. In confluent epithelia, where cell packing fraction is effectively fixed, the prevailing paradigm postulates that fluidity is governed by a geometric shape index determined by the balance of cortical tension and intercellular adhesion. Here, we report that reducing cell-cell adhesion triggers an increase in fluidity with no change in cell shape index, cell density, substrate traction, or junctional line tension. The observed decoupling of shape and fluidity reveals that current vertex models, which treat adhesion as contributing solely to interfacial tension, are incomplete. To reconcile these findings, we extend the theoretical framework to account for the dual nature of adhesion---its thermodynamic role in setting interfacial adhesion energy at the cell-cell junctions and its kinetic role in generating viscous drag due to relative motion between adjacent cells. This generalized model quantitatively captures the experimental data, demonstrating that the interplay between adhesive energy and dissipative friction is essential for epithelial fluidity.

physics.bio-ph↗

arXiv2025

Measurement of tissue viscosity to relate force and motion in collective cell migration

In tissue development, wound healing, and cancer invasion, coordinated cell motion arises from active forces produced by the cells. The relationship between force and motion remains unclear, however, because the forces result from a sum of contributions from activity and the constitutive response of the cell collective. Here, we develop a method to decouple the forces due to activity from those due to constitutive response. As a model of an epithelial tissue, we use a monolayer of epithelial cells in the fluid state, for which the constitutive behavior is that of a viscous fluid. By careful study of the distribution of the ratio between shear stress and strain rate, we show that the order of magnitude of viscosity within the epithelial tissue is 100 Pa-hr and that increasing (decreasing) the actomyosin cytoskeleton and cell-cell adhesions increase (decrease) the magnitude of tissue viscosity. These results establish tissue viscosity as a meaningful way to describe the mechanical behavior of epithelial tissues, and demonstrate a direct relationship between tissue microstructure and material properties. By providing the first experimental measurement of tissue viscosity, our study is a step toward separating the active and constitutive components of stress, in turn clarifying the relationship between force and motion and providing a new means of identifying how active cell forces evolve in space and time.

physics.bio-ph↗

arXiv2025

Energy injection in an epithelial cell monolayer indicated by negative viscosity

Epithelial tissues are driven out of thermodynamic equilibrium by internally generated forces, causing complex patterns of motion. Even when both the forces and motion are measurable, it is not yet possible to relate the two, because the sources of energy injection and dissipation are often unclear. Here, we study how energy is transferred by developing a method to measure the effective viscosity from the shear stresses and strain rates within an epithelial cell monolayer. Interestingly, there emerged multicellular regions in which the relationship between shear stress and shear strain rate was negatively proportional, indicating a negative effective viscosity. The negative effective viscosity occurred in regions wherein cell stresses were less efficient at producing tissue deformations compared to regions of positive effective viscosity. Regions of negative effective viscosity consistently exhibited greater cell speed and vorticity, and the cells had elevated metabolic activity, reflecting an increased energy demand in these cells. Our study shows that negative effective viscosity is a useful means of quantifying the flow of energy in living matter.

physics.bio-ph↗

arXiv2025

Traction and Stress Control Formation and Motion of +1/2 Topological Defects in Epithelial Cell Monolayers

In confluent cell monolayers, patterns of cell forces and motion are systematically altered near topological defects in cell shape. In turn, defects have been proposed to alter cell density, extrusion, and invasion, but it remains unclear how the defects form and how they affect cell forces and motion. Here, we studied +1/2 defects, and, in contrast to prior studies, we observed the concurrent occurrence of both tail-to-head and head-to-tail defect motion in the same cell monolayer. We quantified the cell velocities, the tractions at the cell-substrate interface, and the stresses within the cell layer near +1/2 defects. Results revealed that both traction and stress are sources of activity and dissipation within the epithelial cell monolayer, with the direction of motion of +1/2 defects depending on whether energy is injected by stresses or tractions. Interestingly, patterns of motion, traction, stress, and energy injection near +1/2 defects existed before defect formation, suggesting that defects form as a result of spatially coordinated patterns in cell forces and motion. These findings introduce a new focus, on coordinated patterns of force and motion that lead to defect formation and motion.

physics.bio-ph↗

arXiv2023

Stress-shape misalignment in confluent cell layers

This study investigates the relationship between cell shape and cell-generated stresses in confluent cell layers. Using simultaneous measurements of cell shape orientation and cell-generated contractile forces in MDCK and LP-9 colonies, we report the emergence of correlated, dynamic domains in which misalignment between the directors defined by cell shape and by contractile forces reaches up to 90$^o$, effectively creating extensile domains in a monolayer of contractile cells. To understand this misalignment, we develop a continuum model that decouples the orientation of cell-generated active forces from the orientation of the cell shapes. This challenges the prevailing understanding that cells throughout a tissue create either contractile or extensile forces, and the validity of the usual active nematic models of cell motility where active forces are strictly slaved to cell shape orientation.

physics.bio-ph↗