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Mechanical self organized processes involved in vascular morphogenesis

MSC : Annemiek JM Cornelissen, Marc Durand, Vincent Fleury, Alexis Peaucelle, Camille Gambini, Cecilia Lantos

In many diseases, e.g. cancer, Alzheimer and cardiovascular diseases (hypertension, diabetic retinopathy, etc), adequate vascular growth and/or adaptation are impaired. Understanding how vascular networks form might help to develop better treatment strategies or ways to prevent these diseases.

There is emerging evidence that besides biochemical signaling, vascular morphogenesis is determined by self organized actions of shear stresses generated by the circulating blood (Le Noble et al. 2004, Lucitti et al. 2007) and mechanical stresses generated by the growing, deforming surrounding tissue (Nguyen et al. 2006; Al-Kilani et al. 2008).

To study vascular morphogenesis we have in our laboratory several experimental models available (see figures): the chicken embryo, Physarum Polycephalum (a sizable unicellular organism with a vascular system), and Aurelia Aurita (a jellyfish). The chicken embryo is a classic widely used vasculogenesis model. Aurelia Aurita and Physarum Poly-cephalum are chosen as new biological models to study the self organized actions of mechanical stresses involved in vascular morphogenesis.

In our studies we aim to correlate in vivo observations of vascular morphogenesis with in vivo mechanical measurements of the growing surrounding tissue.

We use different approaches to measure locally visco-elastic properties of tissue: microrheological measurements by introducing (fluorescent/magnetic) microprobes in the extracellular matrix (with Bérengère Abou, CNRS, MSC, Paris), atomic force microscopy, and scanning air puff tonometry. Velocities in the vascular systems are measured using several techniques: contrast speckle velocimetry and stroboscopic velocity measurements (Pries et al. 1994).

Besides experimental techniques, theoretical and mathematical models are developed to analyze and understand the impact of physical parameters on vascular morphogenesis.

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