Mechanics of development and disease


Vito Conte | Junior Group Leader
Agata Nyga | Postdoctoral Researcher

About

In the group we advance cross-disciplinary research at the interface between biology, physics and engineering by studying the mechanical biology and the biological mechanics of pathological development and disease progression.

Specifically, we focus on soft tissue morphogenesis – the process by which a tissue takes or lose shape. Deciphering the physical mechanisms of tissue morphogenesis is a powerful expedient to identify new mechanical hallmarks of cancer progression and define principles of tissue design for organ regeneration. This is so because both healthy and pathological tissues take or lose their shape through processes such as folding, segregation, growth, remodelling and invasion. These are biological processes involving mechanical events that require cells to deform, bear or develop forces as well as to fine-tune their material properties. Deciphering these processes in normal and pathological conditions provides experimental data that can be directly translated into therapeutics targeting diseased cells and tissues at the physical level.

To that end, we are developing new multidisciplinary methods to quantify cell and tissue mechanics in arbitrary 2D and 3D environments that have physiologically-relevant properties. These methods hybridise physical, computational and biological approaches to extract mechanical information from large amounts of experimental data in vitro, in vivo and ex vivo. This data is utilised to identify what mechanical quantities can determine and/or predict cells and tissues dynamics in normal and pathological conditions such as those of carcinogenesis and tumour progression.

 

 

News/Jobs

IBEC at the forefront of research in mechanobiology
20/06/2017

Three IBEC group leaders – Pere Roca-Cusachs, Vito Conte and Xavier Trepat – consolidate the institute’s leadership in mechanobiology by publishing a review of the field in Nature Cell Biology.


IBEC’s newest junior group leader: Vito Conte
15/02/2016

Vito Conte may be familiar to many, having spent more than four years in Xavier Trepat’s Integrative Cell and Tissue Dynamics group, first as a postdoc and later as a Juan de la Cierva fellow. Vito now is a Ramon y Cajal fellow and leads the Mechanics of Development and Disease group, which will take a new direction as he develops new biophysical tools to quantify the mechanics of cell and tissues in 3D environments.


Projects

National projects
CancerMechReg Regulacion biomecanica de la progresion del cancer (2016-2019) MINECO, Proyectos I+D Excelencia Vito Conte

Publications


Rodriguez-Franco, P., Brugués, A., Marin-Llaurado, A., Conte, V., Solanas, G., Batlle, E., Fredberg, J. J., Roca-Cusachs, P., Sunyer, R., Trepat, X., (2017). Long-lived force patterns and deformation waves at repulsive epithelial boundaries Nature Materials 16, (10), 1029-1036

For an organism to develop and maintain homeostasis, cell types with distinct functions must often be separated by physical boundaries. The formation and maintenance of such boundaries are commonly attributed to mechanisms restricted to the cells lining the boundary. Here we show that, besides these local subcellular mechanisms, the formation and maintenance of tissue boundaries involves long-lived, long-ranged mechanical events. Following contact between two epithelial monolayers expressing, respectively, EphB2 and its ligand ephrinB1, both monolayers exhibit oscillatory patterns of traction forces and intercellular stresses that tend to pull cell-matrix adhesions away from the boundary. With time, monolayers jam, accompanied by the emergence of deformation waves that propagate away from the boundary. This phenomenon is not specific to EphB2/ephrinB1 repulsion but is also present during the formation of boundaries with an inert interface and during fusion of homotypic epithelial layers. Our findings thus unveil a global physical mechanism that sustains tissue separation independently of the biochemical and mechanical features of the local tissue boundary.

Keywords: Biological physics, Cellular motility


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.


Perez-Mockus, Gantas, Mazouni, Khalil, Roca, Vanessa, Corradi, Giulia, Conte, Vito, Schweisguth, François, (2017). Spatial regulation of contractility by Neuralized and Bearded during furrow invagination in Drosophila Nature Communications 8, (1), 1594

Embryo-scale morphogenesis arises from patterned mechanical forces. During Drosophila gastrulation, actomyosin contractility drives apical constriction in ventral cells, leading to furrow formation and mesoderm invagination. It remains unclear whether and how mechanical properties of the ectoderm influence this process. Here, we show that Neuralized (Neur), an E3 ubiquitin ligase active in the mesoderm, regulates collective apical constriction and furrow formation. Conversely, the Bearded (Brd) proteins antagonize maternal Neur and lower medial–apical contractility in the ectoderm: in Brd-mutant embryos, the ventral furrow invaginates properly but rapidly unfolds as medial MyoII levels increase in the ectoderm. Increasing contractility in the ectoderm via activated Rho similarly triggers furrow unfolding whereas decreasing contractility restores furrow invagination in Brd-mutant embryos. Thus, the inhibition of Neur by Brd in the ectoderm differentiates the mechanics of the ectoderm from that of the mesoderm and patterns the activity of MyoII along the dorsal–ventral axis.

Keywords: Drosophila, Gastrulation, Morphogenesis


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.



Equipment

  • Mechanical quantification in vitro and in vivo
  • Experimental physical modelling in silico

Collaborations

  • José Muñoz
    Polytechnic University of Catalonia (UPC)