Biology subjects

Ron, J. E.

Publications and source records attributed to Ron, J. E..

5 recordsLinked to original sources

bioRxiv2026

A minimal physical model of adhesion-dependent protrusion explains confined haptotaxis and oscillatory cell migration

Haptotaxis is the directed migration of cells along gradients of substrate adhesion, and is an important guidance mechanism in biology. Recent experiments on fibronectin-patterned tracks show that cells typically migrate toward higher adhesion, then oscillate around the adhesion maximum, with substantial variability in speed and cell length. To explain these cellular shape and migration dynamics we present a minimal model for confined haptotaxis, built around one key physical ingredient: local adhesion strength directly enhances the recruitment of protrusive actin polymerization activity at the cell edge. This coupling creates a front-rear difference in protrusive activity, biasing the cell towards polarization in the direction of the higher adhesion. Quantitative comparison with experiment shows strong agreement at multiple levels: cell population-level directionality statistics and position-dependent changes in cell length and velocity. At the single-cell level, the model reproduces the full diversity of experimentally observed trajectories, including haptotactic bias and its dependence on adhesion-gradient strength, initial position, length and speed variations, myosin II inhibition, and migration on inverted adhesion gradients. Variability in experimental trajectories and migration speed is explained by differences in intrinsic actin polymerization activity and stochastic fluctuations, accounting for the full spectrum of observed migration patterns. Together, our results identify adhesion-dependent amplification of protrusive activity as a minimal and sufficient physical mechanism for understanding haptotaxis.

biophysics↗

bioRxiv2025

Chemotaxis of branched cells in complex environments

Cell migration in vivo is often guided by chemical signals. Such chemotaxis, such as performed by immune cells migrating to a wound site, is complicated by the complex geometry inside living tissues. In this study, we extend our theoretical model of branched-cell migration on a network by introducing chemokine sources to explore the cellular response. The model predicts a speed-accuracy tradeoff, whereby slow cells are significantly more accurate and able to follow efficiently a weak chemoattractant signal. We then compare the models predictions with experimental observations of neutrophils migrating to the site of laser-inflicted wound in a zebrafish larva fin, and migrating in-vitro inside a regular lattice of pillars. We find that the model captures the details of the sub-cellular response to the chemokine gradient, as well as the large-scale migration response. This comparison suggests that the neutrophils behave as fast cells, compromising their chemotaxis accuracy, which explains the functionality of these immune cells.

biophysics↗

bioRxiv2024

Shape dynamics and migration of branched cells on complex networks

Migrating cells often face microenvironmental constraints that force them to extend multiple, often highly dynamic, protrusions, that compete to choose the new direction. However, the analysis of how cells coordinate shape dynamics during this directional decision-making process has been restricted to single junctions. Here, we present a theoretical model and the corresponding experimental proof of concept using in vivo and in vitro live-cell microscopy and a neuronal network-based image analysis pipeline, to explore the shape and migration dynamics of highly bifurcated cells during spontaneous random migration. We found that macrophages and endothelial cells display different migration regimes in a hexagonal adhesive network, despite sharing a mesenchymal migratory strategy. Macrophages moved faster and presented larger changes in cell length in comparison to endothelial cells. The theoretical model describes the behavior of both cells during directional decision-making, and it reveals a trade-off between exploration for directional cues and long-range migration efficiency, showing the fine tune regulation of shape dynamics in complex geometries. TeaserHighly branched cells require precise control of their shape dynamics to ensure microenvironment exploration while keeping their motility.

biophysics↗

bioRxiv2023

Polarization and motility of one-dimensional multi-cellular trains

Collective cell migration, whereby cells adhere to form multi-cellular clusters that move as a single entity, play an important role in numerous biological processes, such as during development and cancer progression. Recent experimental work focused on migration of one-dimensional cellular clusters, confined to move along adhesive lanes, as a simple geometry in which to systematically study this complex system. One-dimensional migration also arises in the body when cells migrate along blood vessels, axonal projections and narrow cavities between tissues. We explore here the modes of one-dimensional migration of cellular clusters ("trains"), by implementing cell-cell interactions in a model of cell migration that contains a mechanism for spontaneous cell polarization. We go beyond simple phenomenological models of the cells as self-propelled particles, by having the internal polarization of each cell depend on its interactions with the neighboring cells, that directly affect the actin polymerization activity at the cells leading edges. Both Contact Inhibition of Locomotion (CIL) and Cryptic Lamellipodia (CL) interactions between neighboring cells are introduced. We find that this model predicts multiple motility modes of the cell trains, that can have several different speeds for the same polarization pattern. Comparing to experimental data we find that MDCK cells are poised along the transition region where CIL and CL roughly balance each other, where collective migration speed is most sensitive to the values of the cell-cell interaction strength.

biophysics↗

bioRxiv2022

Emergent oscillations during cellular directional decision-making on junctions

Motile cells inside living tissues often encounter junctions, where their path branches into several alternative directions of migration. We present a theoretical model of cellular polarization for cells migrating along one-dimensional lines, arriving at a symmetric Y-junction and extending protrusions along the different paths that emanate from the junction. The model predicts the spontaneous emergence of deterministic oscillations between competing protrusions, whereby the cellular polarization and growth alternates between the competing protrusions. The oscillations are modified by cellular noise, but remain as a dominant feature which affects the time it takes the cell to migrate across the junction. These predicted oscillations in the cellular polarization during the directional decision making process at the junction are found experimentally for two different cell types, non-cancerous endothelial and cancerous glioma cells, migrating on patterned network of thin adhesive lanes with junctions.

biophysics↗