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Irina Pi-Jaumà

Publications and source records attributed to Irina Pi-Jaumà.

3 recordsLinked to original sources

Bistability of cellular traction on strain-stiffening substrates

To migrate, cells exert traction forces on the extracellular matrix (ECM) -- a biopolymer network that often exhibits nonlinear strain-stiffening elasticity. Cellular tractions can therefore stiffen the ECM. At the same time, cells exert stronger tractions on stiffer ECM. Here, we show theoretically that this traction-stiffness feedback can produce traction bistability and hysteresis. As a result, increasing either the ECM's nonlinear elasticity or cellular contractility leads to a discontinuous transition from low to high tractions. This traction jump might trigger collective cell migration as the ECM stiffens, for example during development and tumor progression. Moreover, the bistable behavior might provide robustness to cellular traction forces when cells migrate through mechanically heterogeneous environments.

physics.bio-ph↗

Cell clusters sense their global shape to drive collective migration

The collective migration of epithelial groups of cells plays a central role in processes such as embryo development, wound healing, and cancer invasion. While finite cell clusters are known to collectively migrate in response to external gradients, the competing effect of possible endogenous cues is largely unknown.Here, we demonstrate that the polarization of peripheral cells that pull the cluster's edge outward is sufficient to induce and sustain the collective migration of confluent clusters. We use a general continuum model to show that the underlying shape-sensing mechanism is purely mechanical, relying on long-range hydrodynamic interactions and cell-cell alignment forces. As a proof-of-concept, we validate our findings with experiments on monolayer clusters from various cell lines, where we control initial shapes and sizes. The mechanism operates independently of external signals and will generally interfere with them. Specifically, we predict and observe experimentally that it can override collective durotaxis, reversing the direction of migration. Together, our results offer a physical framework for understanding how cell interactions govern the interplay between global shape and collective motion and afford engineering principles for optimal control and manipulation of cell cluster shape and motion.

physics.bio-ph↗

Collective durotaxis of cohesive cell clusters on a stiffness gradient

Many types of motile cells perform durotaxis, namely, directed migration following gradients of substrate stiffness. Recent experiments have revealed that cell monolayers can migrate toward stiffer regions even when individual cells do not -- a phenomenon known as collective durotaxis. Here we address the spontaneous motion of finite cohesive cell monolayers on a stiffness gradient. We theoretically analyze a continuum active polar fluid model that has been tested in recent wetting assays of epithelial tissues, and includes two types of active forces (cell-substrate traction and cell-cell contractility). The competition between the two active forces determines whether a cell monolayer spreads or contracts. Here, we show that this model generically predicts collective durotaxis, and that it features a variety of dynamical regimes as a result of the interplay between the spreading state and the global propagation, including sequential contraction and spreading of the monolayer as it moves toward higher stiffness. We solve the model exactly in some relevant cases, which provides both physical insights into the mechanisms of tissue durotaxis and spreading as well as a variety of predictions that could guide the design of future experiments.

physics.bio-ph↗