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 engineering, biology and physics. We are interested in deciphering the physical mechanisms of development and disease in biological organisms.

We do so by studying how cell and tissue mechanics determine structure and function in these organisms. To that end, we are developing new biophysical tools to compute cell and tissue forces in arbitrary 3D environments that have realistic geometries and material properties, such as anisotropy, heterogeneity, poroelasticity, and non-linear viscoelasticity. We utilise these tools to carry out in vivo and in vitro mechanical measurements, which we integrate into 2D and 3D physical models of the biological organisms under study. The in silico models we build allow us to make predictive biomechanical analyses of these organisms by studying the necessary and sufficient conditions for their development and disease under conditions very close to the real ones.

The group currently has two main fields of research inside IBEC’s Bioengineering for Future Medicine pillar.

Biomechanical regulation of cancer progression
Our research in this field moves from growing evidence that cancer progression alters mechanical properties of cells and tissues affected by the disease. However, we ignore whether these alterations feed back into the cancer progression and, for that reason, may represent potential means to hinder or arrest the disease biomechanically. We want to understand the interplay between mechanics and malignancy of tissues to help identify new biomechanical markers or physical mechanisms of cancer progression that are clinically targetable for the prevention and treatment of the disease.

Embryo morphogenesis
In 2016 we started to explore how cell and tissue mechanics in the early embryo are associated to and regulated by a concerted programme of gene expression. This programme transforms the embryo from a simple unstructured organism into a healthy complex organism. Specifically, we’re interested in quantifying the forces defining the physical mechanisms that morph the fruit fly blastula into the gastrula. Gastrulation is a key stage in the healthy development of the embryo of most animals: if anything goes awry during this process a diseased or abormal phenotype is produced if the embryo survives at all.

Right: In vivo biomechanical quantification of ventral furrow invagination in the Drosophila melanogaster embryo.

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.


POSTDOC opportunity in collaboration with the EMBL – Heidelberg
Application Deadline: 14/09/2017

The Mechanics of Development and Disease group is calling for postdoctoral candidates to apply to the EMBL Interdisciplinary Postdocs (EIPOD) programme 2017. The postdoctoral research project will be carried out at the EMBL in external collaboration with the groups of Prof Maria Leptin and Dr Diz-Muñoz.

Interested candidates may find further details on the postdoctoral programme at this link.

PROJECT DESCRIPTION
The healthy development of an embryo requires epithelia to migrate and reshape to different extents in order to serve specific functions in a system of increasing complexity. If the dynamics of such processes goes awry then specific biomechanical function will not follow suit and diseased abnormal phenotype may arise. Biomechanical epithelial function requires both force generation and stress transmission to create, sustain and coordinate motion at the cellular and tissue levels of the embryo. However, the active generation of cellular forces may only lead to embryonic growth and form if force is modulated and transmitted across tissues over time, a process that is mediated by the compliance of embryonic tissues to deformation. Therefore, the question of tissue compliance and, more generally, that of the material properties of embryonic tissues are becoming as relevant as that of force generation to the understanding of embryo morphogenesis as a three-dimensional phenomenon. In that regard, this EIPOD research project will combine in vivo experimentation and in silico simulation to assess how the material properties of the late Drosophila blastula combine to create a biophysical landscape that, to some extent, may energetically prepattern the morphogenetic movements transforming the blastula in a multi-layered gastrula.


PhD Position in Cancer Biomechanics
Application Deadline: 31/08/2017

The Mechanics of Development and Disease group at the Institute for Bioengineering of Catalonia (IBEC) is looking for a PhD candidate PhD student on a scholarship funded by the Spanish Ministry of Economy, Industry and Competitivity (MINECO) through its Spanish National Training Program for Doctoral Researchers (Subprograma de Formación de Personal Investigador).


Call for POSTDOCTORAL candidates in collaboration with the EMBL – Heidelberg
15/06/2017

The Mechanics of Development and Disease group is calling for postdoctoral candidates to apply to the EMBL Interdisciplinary Postdocs (EIPOD) programme 2017. The postdoctoral research project will be carried out at the EMBL in external collaboration with the groups of Prof Maria Leptin and Dr Diz-Muñoz.

Interested candidates may find further details on the postdoctoral programme at this link. For further details about the project, please check the JOBS tab.


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


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.



Equipment

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

Collaborations

  • José Muñoz
    Polytechnic University of Catalonia (UPC)

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