Sprouting angiogenesis, where new blood vessels grow from pre-existing ones, is a complex process where biochemical and mechanical signals regulate endothelial cell proliferation and movement. Therefore, a mathematical description of sprouting angiogenesis has to take into consideration biological signals as well as relevant physical processes, in particular the mechanical interplay between adjacent endothelial cells and the extracellular microenvironment. In this work, we introduce the first phase-field continuous model of sprouting angiogenesis capable of predicting sprout morphology as a function of the elastic properties of the tissues and the traction forces exerted by the cells. The model is very compact, only consisting of three coupled partial differential equations, and has the clear advantage of a reduced number of parameters. This model allows us to describe sprout growth as a function of the cell-cell adhesion forces and the traction force exerted by the sprout tip cell. In the absence of proliferation, we observe that the sprout either achieves a maximum length or, when the traction and adhesion are very large, it breaks. Endothelial cell proliferation alters significantly sprout morphology, and we explore how different types of endothelial cell proliferation regulation are able to determine the shape of the growing sprout. The largest region in parameter space with well formed long and straight sprouts is obtained always when the proliferation is triggered by endothelial cell strain and its rate grows with angiogenic factor concentration. We conclude that in this scenario the tip cell has the role of creating a tension in the cells that follow its lead. On those first stalk cells, this tension produces strain and/or empty spaces, inevitably triggering cell proliferation. The new cells occupy the space behind the tip, the tension decreases, and the process restarts.
Our results highlight the ability of mathematical models to suggest relevant hypotheses with respect to the role of forces in sprouting, hence underlining the necessary collaboration between modelling and molecular biology techniques to improve the current state-of-the-art.
The root-knot nematode (RKN) Meloidogyne luci is included in the Alert List of the European Plant Protection Organization, because it has potential negative impacts on economically important crops. Identification of plant species/cultivars resistant to M. luci is important for its management. Susceptibility of 35 commercial plant species/cultivars, from nine families to a M. luci isolate from Portugal was evaluated in pot assays, assessing root gall index (GI) and reproduction factor (Rf) 60 d after inoculation, with tomato ‘Coração-de-Boi’ used as the positive susceptible experimental control. Presence/absence of RKN resistance genes was also determined in the tomato and pepper cultivars. One cultivar of cabbage, three of lettuce, ten of pepper, one of sugar beet, and all the cultivars of Cucurbitaceae (five), Fabaceae (two) and Poaceae (one) were susceptible to M. luci (GI = 4-5; Rf = 2.1-152.3). One cultivar each of carrot, passion fruit, lettuce ‘Cocktail’, cabbage ‘Bacalan’, ‘Coração’ and ‘Lombarda’, and spinach ‘Tayto’ were resistant/hypersensitive (Rf < 1; GI > 2). The tomato ‘Actimino’, ‘Briomino’, ‘Veinal’ and ‘Vimeiro’, which carried at least one copy of the Mi-1.2 gene, were resistant to the nematode (GI = 1-2; 0.0 < Rf < 0.1). These results indicate that the tomato cultivars have potential to contribute to reduction of M. luci populations in agro-ecosystems and improve the crop yields.
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