Biology subjects

Fortunato, I. C.

Publications and source records attributed to Fortunato, I. C..

3 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↗

bioRxiv2024

Single cell migration along and against confined haptotactic gradients

Directed cell migration along gradients of extracellular matrix (ECM) density -a process called haptotaxis- plays a central role in morphogenesis, the immune response, and cancer invasion. It is commonly assumed that cells respond to these gradients by migrating directionally towards the regions of highest ligand density. In contrast with this view, here we show that cells exposed to micropatterned fibronectin gradients exhibit a complex repertoire of trajectories, including directed haptotactic migration up the gradient but also linear oscillations and circles with extended periods of migration down the gradient. To explain this behavior, we developed a biophysical model of haptotactic cell migration based on a coarse-grained molecular clutch model coupled to persistent stochastic polarity dynamics. While initial haptotactic migration is explained by the differential friction at the front and back of the cell, the observed complex trajectories over longer time scales arise from the interplay between differential friction, persistence, and physical confinement. Overall, our study reveals that confinement and persistence modulate the ability of cells to sense and respond to haptotactic cues and provides a framework to understand how cells navigate complex environments.

cell biology↗

bioRxiv2022

Stiffness-dependent active wetting enables optimal collective cell durotaxis

The directed migration of cellular clusters enables morphogenesis, wound healing, and collective cancer invasion. Gradients of substrate stiffness are known to direct the migration of cellular clusters in a process called collective durotaxis, but underlying mechanisms remain unclear. Here, we unveil a connection between collective durotaxis and the wetting properties of cellular clusters. We show that clusters of cancer cells dewet soft substrates and wet stiff ones. At intermediate stiffness, at the crossover from low to high wettability, clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient, and actomyosin activity. We demonstrate this behavior on substrates coated with the cell-cell adhesion protein E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop a physical model of three-dimensional active wetting that explains this mode of collective durotaxis in terms of a balance between in-plane active traction and tissue contractility, and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a physical mechanism of collective durotaxis, through both cell-cell and cell-substrate adhesion ligands, based on the wetting properties of active droplets.

biophysics↗