Biology subjects

Sunyer, R.

Publications and source records attributed to Sunyer, R..

6 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↗

bioRxiv2026

Physiomimetic culture bias durotaxis toward soft environments

Directed cell migration underlies many biological phenomena, from embryonic development to tumor metastasis and organ fibrosis. Most cells typically migrate toward stiffer regions of their extracellular matrix -a behavior known as positive durotaxis. Here we show that culture on rigid plastic reinforces this response, whereas preconditioning in soft 3D physiomimetic environments reprograms migration towards softer environments, a phenomenon known as negative durotaxis. Fetal rat lung fibroblasts preconditioned in 3D physiomimetic hydrogels exhibited negative durotaxis and accumulated near [~]5 kPa, corresponding to the physiological stiffness of the lung. In contrast, genetically identical cells maintained on conventional 2D plastic substrates migrated up stiffness gradients, toward stiffer regions. Although both populations displayed a biphasic force-stiffness relationship, they differed in force magnitude and cytoskeletal organization. Molecular-clutch modeling revealed that durotaxis reversal emerges from two distinct mechanical regimes: a mechanosensitive, high-motor-clutch state that stabilizes adhesions on stiff substrates and drives positive durotaxis, and a low-motor, weak-adhesion state in which clutch slippage on the stiff side causes negative durotaxis. Our results show that durotaxis direction is not an intrinsic cellular property. Rather, it emerges from the interplay between motor activity and adhesion dynamics and can be tuned by culture conditions.

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↗

bioRxiv2022

Mapping mechanical stress in curved epithelia of designed size and shape

The function of organs such as lungs, kidneys and mammary glands relies on the three-dimensional geometry of their epithelium. To adopt shapes such as spheres, tubes and ellipsoids, epithelia generate mechanical stresses that are generally unknown. Here we engineered curved epithelial monolayers of controlled size and shape and mapped their state of stress. We designed pressurized epithelia with circular, rectangular and ellipsoidal footprints. We developed a computational method to map the stress tensor in these epithelia. This method establishes a direct correspondence between epithelial shape and mechanical stress without assumptions of material properties. In epithelia with spherical geometry spanning more than one order of magnitude in radius, we show that stress weakly increases with areal strain in a size-independent manner. In epithelia with rectangular and ellipsoidal cross-section we found pronounced stress anisotropies consistent with the asymmetric distribution of tractions measured at the cell-substrate contact line. In these anisotropic profiles, cell shape tended to align with the direction of maximum principal stress but this alignment was non-universal and depended on epithelial geometry. Besides interrogating the fundamental mechanics of epithelia over a broad range of sizes and shapes, our approach will enable a systematic study of how geometry and stress influence epithelial fate and function in three-dimensions.

biophysics↗

bioRxiv2021

Involvement of mechanical cues in the migration of Cajal-Retzius cells in the marginal zone during neocortical development

Emerging evidence points to coordinated action of chemical and mechanical cues during brain development. At early stages of neocortical development, angiogenic factors and chemokines such as CXCL12, ephrins, and semaphorins assume crucial roles in orchestrating neuronal migration and axon elongation of postmitotic neurons. Here we explore the intrinsic mechanical properties of the developing marginal zone of the pallium in the migratory pathways and brain distribution of the pioneer Cajal-Retzius cells. These pioneer neurons are generated in several proliferative regions in the developing brain (e.g., the cortical hem and the pallial subpallial boundary) and migrate tangentially in the preplate/marginal zone covering the upper portion of the neocortex. These cells play crucial roles in correct neocortical layer formation by secreting several molecules such as Reelin. Our results indicate that the motogenic properties of Cajal-Retzius cells and their perinatal distribution in the marginal zone are also modulated by both chemical and mechanical factors, by the specific mechanical properties of Cajal-Retzius cells, and by the differential stiffness of the migratory routes. Indeed, cells originating in the cortical hem display higher migratory capacities than those generated in the pallial subpallial boundary which may be involved in the differential distribution of these cells in the dorsal-lateral axis in the developing marginal zone.

neuroscience↗