Kalukula, Y. | Search bioRxiv

bioRxiv2024

The actin cortex acts as a mechanical memory of morphology in confined migrating cells

Cell migration in narrow microenvironments is a hallmark of numerous physiological processes, involving successive cycles of confinement and release that drive significant morphological changes. However, it remains unclear whether migrating cells can retain a memory of their past morphological states, which could potentially enhance their navigation through confined spaces. By combining cell migration assays on standardized microsystems with biophysical modeling and biochemical perturbations, we demonstrate that local geometry governs these morphological switches, thereby facilitating cell passage through long and narrow gaps. We uncovered a long-term memory of past confinement events in migrating cells, with morphological states correlated across transitions through actin cortex remodeling. These findings suggest that mechanical memory in migrating cells plays an active role in their migratory potential in confined environments.

biophysics↗

bioRxiv2022

Geometry-driven migration efficiency of minimal cell clusters

The directed migration of epithelial cell collectives through coordinated movements plays a crucial role in various physiological and pathological processes and is increasingly understood at the level of large confluent monolayers. However, numerous processes rely on the migration of small groups of polarized epithelial clusters in complex environments, and their responses to external geometries remain poorly understood. To address this, we cultivated primary epithelial keratocyte tissues on adhesive microstripes, creating autonomous epithelial clusters with well-defined geometries. We showed that their migration efficiency is strongly influenced by the contact geometry, and the orientation of cell-cell contacts with respect to the direction of migration. To elucidate the underlying mechanisms, we systematically explored possible cell-cell interactions using a minimal active matter model. Our investigations revealed that a combination of velocity and polarity alignment with contact regulation of locomotion captures the experimental data, which we then validated via force and intracellular stress measurements. Furthermore, we predict that this combination of rules enables efficient navigation in complex geometries, which we confirm experimentally. Altogether, our findings provide a conceptual framework for extracting interaction rules governing the behavior of active systems interacting with physical boundaries, as well as designing principles for collective navigation in complex microenvironments.

biophysics↗