Abstract: Cell migration along gradients of extracellular matrix (ECM) properties, such as stiffness and protein density, is crucial in processes like development, immune response, fibrosis, and cancer. Two key migration phenomena—durotaxis and haptotaxis—demonstrate how cells navigate in response to mechanical and density cues in the ECM. Durotaxis describes the migration of cells towards regions of higher substrate stiffness. In 2016, we discovered that cell clusters exhibit a form of collective durotaxis, moving together towards stiffer regions even when individual cells do not. This phenomenon, dependent on myosin-mediated force transmission, was observed across various epithelial cell types in vitro. Subsequent in vivo studies by R. Mayor’s group on Neural Crest cell migration in Xenopus embryos corroborated collective durotaxis but highlighted differences in migration modes, with clusters moving cohesively in vivo and asymmetrically in vitro. Our experiments on E-cadherin-coated substrates suggest that a balance between cluster contractility and adhesion switch between these two modes of durotaxis, revealing a mechanism to control the collective migration. But cells can also follow ECM protein density gradients, a phenomenon called haptotaxis. 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, we have found 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 these complex patterns, we developed a biophysical model that integrates a molecular clutch mechanism with stochastic cell polarity dynamics. The model reveals that haptotactic migration is influenced not only by frictional asymmetries along the cell’s front and rear but also by persistence and physical confinement, which modulate cell responses to ECM density cues. Together, these findings underscore how the physical and chemical properties of the ECM regulate cell migration in development, immunity, and cancer. They also provide insights into how environmental factors influence both single-cell and collective migration, suggesting potential strategies to modulate cellular behavior in pathological contexts.
Bio: Raimon Sunyer is a biophysicist specializing in mechanobiology. He earned both his B.Sc. and Ph.D. in physics from the University of Barcelona (UB), completing his doctoral studies under the guidance of Daniel Navajas and Felix Ritort. He then completed two postdoctoral fellowships: the first at the National Institutes of Health (NIH, Bethesda, MD) with R. Nossal and D. Sackett, and the second at the Institute for Bioengineering of Catalonia (IBEC) with X. Trepat. In 2019, he established his own research group, supported initially by a Young Researcher’s grant, followed by a Ramon y Cajal fellowship, and later, an assistant professor position at the University of Barcelona. Based at the Medical School on the Hospital Clinic of Barcelona campus, Sunyer’s lab investigates how cells detect and respond to mechanical signals across various biological scenarios, including development, fibrosis, and cancer. His team employs a range of biophysical techniques—such as traction force microscopy, micropatterning, microfluidics, hydrogel stiffness gradients, and Atomic Force Microscopy—alongside molecular biology, advanced optical microscopy, and computational modeling to explore these mechanobiological processes.
Host: Yun Chen