Staff member

Vito Conte

Junior Group Leader
Mechanics of Development and Disease
+34 934 020 284
CV Summary

Vito is a scientist in bioengineering and biophysics. He received his MPhys in Theoretical Physics cum laude from the University of Naples Federico II and his PhD in computational biomechanics from King's College London in 2009 under the supervision of Mark Miodownik. He continued investigating as a postdoctoral researcher in the Miodownik group until 2011 before joining as a postdoctoral researcher the Integrative Cell and Tissue Dynamics Group led by Xavier Trepat at the Institute of Bioengineering of Catalonia (IBEC) in Barcelona until 2015. Vito became a Ramon-y-Cajal fellow and Junior PI at the IBEC in 2016. His investigations aim at understanding the physical mechanisms of development and disease in biological organisms through multidisciplinary approaches combining in vivo, in vitro and in silico techniques.

Staff member publications

Roca-Cusachs, Pere, Conte, Vito, Trepat, Xavier, (2017). Quantifying forces in cell biology Nature Cell Biology 19, (7), 742-751

Cells exert, sense, and respond to physical forces through an astounding diversity of mechanisms. Here we review recently developed tools to quantify the forces generated by cells. We first review technologies based on sensors of known or assumed mechanical properties, and discuss their applicability and limitations. We then proceed to draw an analogy between these human-made sensors and force sensing in the cell. As mechanics is increasingly revealed to play a fundamental role in cell function we envisage that tools to quantify physical forces may soon become widely applied in life-sciences laboratories.

Sunyer, R., Conte, V., Escribano, J., Elosegui-Artola, A., Labernadie, A., Valon, L., Navajas, D., García-Aznar, J. M., Muñoz, J. J., Roca-Cusachs, P., Trepat, X., (2016). Collective cell durotaxis emerges from long-range intercellular force transmission Science 353, (6304), 1157-1161

The ability of cells to follow gradients of extracellular matrix stiffness-durotaxis-has been implicated in development, fibrosis, and cancer. Here, we found multicellular clusters that exhibited durotaxis even if isolated constituent cells did not. This emergent mode of directed collective cell migration applied to a variety of epithelial cell types, required the action of myosin motors, and originated from supracellular transmission of contractile physical forces. To explain the observed phenomenology, we developed a generalized clutch model in which local stick-slip dynamics of cell-matrix adhesions was integrated to the tissue level through cell-cell junctions. Collective durotaxis is far more efficient than single-cell durotaxis; it thus emerges as a robust mechanism to direct cell migration during development, wound healing, and collective cancer cell invasion.

Bazellières, Elsa, Conte, Vito, Elosegui, Alberto, Serra-Picamal, Xavier, Bintanel-Morcillo, María, Roca-Cusachs, Pere, Muñoz, José J., Sales-Pardo, Marta, Guimerà, Roger, Trepat, Xavier, (2015). Control of cell-cell forces and collective cell dynamics by the intercellular adhesome Nature Cell Biology 17, (4), 409-420

Dynamics of epithelial tissues determine key processes in development, tissue healing and cancer invasion. These processes are critically influenced by cell–cell adhesion forces. However, the identity of the proteins that resist and transmit forces at cell–cell junctions remains unclear, and how these proteins control tissue dynamics is largely unknown. Here we provide a systematic study of the interplay between cell–cell adhesion proteins, intercellular forces and epithelial tissue dynamics. We show that collective cellular responses to selective perturbations of the intercellular adhesome conform to three mechanical phenotypes. These phenotypes are controlled by different molecular modules and characterized by distinct relationships between cellular kinematics and intercellular forces. We show that these forces and their rates can be predicted by the concentrations of cadherins and catenins. Unexpectedly, we identified different mechanical roles for P-cadherin and E-cadherin; whereas P-cadherin predicts levels of intercellular force, E-cadherin predicts the rate at which intercellular force builds up.

Serra-Picamal, Xavier, Conte, Vito, Sunyer, Raimon, Muñoz, José J., Trepat, Xavier, (2015). Mapping forces and kinematics during collective cell migration Methods in Cell Biology - Biophysical Methods in Cell Biology (ed. Wilson, L., Tran, P.), Academic Press (Santa Barbara, USA) 125, 309-330

Abstract Fundamental biological processes including morphogenesis and tissue repair require cells to migrate collectively. In these processes, epithelial or endothelial cells move in a cooperative manner coupled by intercellular junctions. Ultimately, the movement of these multicellular systems occurs through the generation of cellular forces, exerted either on the substrate via focal adhesions (cell–substrate forces) or on neighboring cells through cell–cell junctions (cell–cell forces). Quantitative measurements of multicellular forces and kinematics with cellular or subcellular resolution have become possible only in recent years. In this chapter, we describe some of these techniques, which include particle image velocimetry to map cell velocities, traction force microscopy to map forces exerted by cells on the substrate, and monolayer stress microscopy to map forces within and between cells. We also describe experimental protocols to perform these measurements. The combination of these techniques with high-resolution imaging tools and molecular perturbations will lead to a better understanding of the mechanisms underlying collective cell migration in health and disease.

Keywords: Collective cell migration, Monolayer stress microscopy, Traction force microscopy

Brugués, A., Anon, E., Conte, V., Veldhuis, J. H., Gupta, M., Colombelli, J., Muñoz, J. J., Brodland, G. W., Ladoux, B., Trepat, X., (2014). Forces driving epithelial wound healing Nature Physics 10, (9), 683–690

A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and 'purse-string' contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate.

Muñoz, J. J., Conte, V., Asadipour, N., Miodownik, M., (2013). A truss element for modelling reversible softening in living tissues Mechanics Research Communications 49, 44-49

We resort to non-linear viscoelasticity to develop a truss element able to model reversible softening in lung epithelial tissues undergoing transient stretch. Such a Maxwell truss element is built by resorting to a three-noded element whose mid-node is kinematically constrained to remain on the line connecting the end-nodes. The whole mechanical system undergoes an additive decomposition of the strains along the truss direction where the total contribution of the mid-node is accounted for by using a null-space projection and static condensation techniques. Assembling of such line-elements in 3D networks allows us to model extended regions of living tissues as well as their anisotropies.

Keywords: Maxwell, Null-space, Reversible softening, Truss, Viscoelasticity

Serra-Picamal, Xavier, Conte, Vito, Vincent, Romaric, Anon, Ester, Tambe, Dhananjay T., Bazellieres, Elsa, Butler, James P., Fredberg, Jeffrey J., Trepat, Xavier, (2012). Mechanical waves during tissue expansion Nature Physics Nature Publishing Group 8, (8), 628-634

The processes by which an organism develops its shape and heals wounds involve expansion of a monolayer sheet of cells. The mechanism underpinning this epithelial expansion remains obscure, despite the fact that its failure is known to contribute to several diseases, including carcinomas, which account for about 90% of all human cancers. Here, using the micropatterned epithelial monolayer as a model system, we report the discovery of a mechanical wave that propagates slowly to span the monolayer, traverses intercellular junctions in a cooperative manner and builds up differentials of mechanical stress. Essential features of this wave generation and propagation are captured by a minimal model based on sequential fronts of cytoskeletal reinforcement and fluidization. These findings establish a mechanism of long-range cell guidance, symmetry breaking and pattern formation during monolayer expansion.

Keywords: Biological physics

Conte, Vito, Ulrich, Florian, Baum, Buzz, Muñoz, Jose, Veldhuis, Jim, Brodland, Wayne, Miodownik, Mark, (2012). A biomechanical analysis of ventral furrow formation in the Drosophila Melanogaster Embryo PLoS ONE Public Library of Science 7, (4), e34473

The article provides a biomechanical analysis of ventral furrow formation in the Drosophila melanogaster embryo. Ventral furrow formation is the first large-scale morphogenetic movement in the fly embryo. It involves deformation of a uniform cellular monolayer formed following cellularisation, and has therefore long been used as a simple system in which to explore the role of mechanics in force generation. Here we use a quantitative framework to carry out a systematic perturbation analysis to determine the role of each of the active forces observed. The analysis confirms that ventral furrow invagination arises from a combination of apical constriction and apical–basal shortening forces in the mesoderm, together with a combination of ectodermal forces. We show that the mesodermal forces are crucial for invagination: the loss of apical constriction leads to a loss of the furrow, while the mesodermal radial shortening forces are the primary cause of the internalisation of the future mesoderm as the furrow rises. Ectodermal forces play a minor but significant role in furrow formation: without ectodermal forces the furrow is slower to form, does not close properly and has an aberrant morphology. Nevertheless, despite changes in the active mesodermal and ectodermal forces lead to changes in the timing and extent of furrow, invagination is eventually achieved in most cases, implying that the system is robust to perturbation and therefore over-determined.

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