14 research outputs found
Colloquium: Mechanical formalisms for tissue dynamics
The understanding of morphogenesis in living organisms has been renewed by
tremendous progressin experimental techniques that provide access to
cell-scale, quantitative information both on theshapes of cells within tissues
and on the genes being expressed. This information suggests that
ourunderstanding of the respective contributions of gene expression and
mechanics, and of their crucialentanglement, will soon leap forward.
Biomechanics increasingly benefits from models, which assistthe design and
interpretation of experiments, point out the main ingredients and assumptions,
andultimately lead to predictions. The newly accessible local information thus
calls for a reflectionon how to select suitable classes of mechanical models.
We review both mechanical ingredientssuggested by the current knowledge of
tissue behaviour, and modelling methods that can helpgenerate a rheological
diagram or a constitutive equation. We distinguish cell scale ("intra-cell")and
tissue scale ("inter-cell") contributions. We recall the mathematical framework
developpedfor continuum materials and explain how to transform a constitutive
equation into a set of partialdifferential equations amenable to numerical
resolution. We show that when plastic behaviour isrelevant, the dissipation
function formalism appears appropriate to generate constitutive equations;its
variational nature facilitates numerical implementation, and we discuss
adaptations needed in thecase of large deformations. The present article
gathers theoretical methods that can readily enhancethe significance of the
data to be extracted from recent or future high throughput
biomechanicalexperiments.Comment: 33 pages, 20 figures. This version (26 Sept. 2015) contains a few
corrections to the published version, all in Appendix D.2 devoted to large
deformation
Morphological instabilities of stratified epithelia: a mechanical instability in tumour formation
The role of fluctuations and stress on the effective viscosity of cell aggregates
Cell aggregates are a tool for in vitro studies of morphogenesis, cancer invasion, and tissue engineering. They respond to mechanical forces as a complex rather than simple liquid. To change an aggregate's shape, cells have to overcome energy barriers. If cell shape fluctuations are active enough, the aggregate spontaneously relaxes stresses (“fluctuation-induced flow”). If not, changing the aggregate's shape requires a sufficiently large applied stress (“stress-induced flow”). To capture this distinction, we develop a mechanical model of aggregates based on their cellular structure. At stress lower than a characteristic stress τ*, the aggregate as a whole flows with an apparent viscosity η*, and at higher stress it is a shear-thinning fluid. An increasing cell–cell tension results in a higher η* (and thus a slower stress relaxation time tc). Our constitutive equation fits experiments of aggregate shape relaxation after compression or decompression in which irreversibility can be measured; we find tc of the order of 5 h for F9 cell lines. Predictions also match numerical simulations of cell geometry and fluctuations. We discuss the deviations from liquid behavior, the possible overestimation of surface tension in parallel-plate compression measurements, and the role of measurement duration
Soluble VE-cadherin in metastatic breast cancer: an independent prognostic factor for both progression-free survival and overall survival
International audiencePatients with metastatic breast cancer (MBC) represent a heterogeneous group, with large differences in outcomes from individual patients. VE-cadherin, an endothelial-specific cadherin, was shown to promote tumour proliferation and angiogenesis. Soluble VE-cadherin has been recently associated to breast cancer progression. This study was designed to investigate the prognosis significance of soluble VE-cadherin in hormone-refractory MBC
The tyrosine-kinase inhibitor sunitinib targets vascular endothelial (VE)-cadherin: a marker of response to antitumoural treatment in metastatic renal cell carcinoma
International audienceVascular endothelial (VE)-cadherin is an endothelial cell-specific protein responsible for endothelium integrity. Its adhesive properties are regulated by post-translational processing, such as tyrosine phosphorylation at site Y685 in its cytoplasmic domain, and cleavage of its extracellular domain (sVE). In hormone-refractory metastatic breast cancer, we recently demonstrated that sVE levels correlate to poor survival. In the present study, we determine whether kidney cancer therapies had an effect on VE-cadherin structural modifications and their clinical interest to monitor patient outcome