Escultura de órgãos por rigidez da matriz extracelular padronizada: mero acaso, fortuita necessidade ou design inteligente???

terça-feira, dezembro 12, 2017

Organ sculpting by patterned extracellular matrix stiffness

Justin Crest Alba Diz-Muñoz Dong-Yuan Chen Daniel A Fletcher David Bilder Is a corresponding author

University of California-Berkeley, United States


A mechanical stiffness gradient in the follicle basement membrane.


How organ-shaping mechanical imbalances are generated is a central question of morphogenesis, with existing paradigms focusing on asymmetric force generation within cells. We show here that organs can be sculpted instead by patterning anisotropic resistance within their extracellular matrix (ECM). Using direct biophysical measurements of elongating Drosophila egg chambers, we document robust mechanical anisotropy in the ECM-based basement membrane (BM) but not in the underlying epithelium. Atomic force microscopy (AFM) on wild-type BM in vivo reveals an anterior–posterior (A–P) symmetric stiffness gradient, which fails to develop in elongation-defective mutants. Genetic manipulation shows that the BM is instructive for tissue elongation and the determinant is relative rather than absolute stiffness, creating differential resistance to isotropic tissue expansion. The stiffness gradient requires morphogen-like signaling to regulate BM incorporation, as well as planar-polarized organization to homogenize it circumferentially. Our results demonstrate how fine mechanical patterning in the ECM can guide cells to shape an organ.

eLife digest

All organs have specific shapes and architectures that are necessary for them to work properly. Many different factors are responsible for arranging the right cells into the correct positions to make an organ. These include physical forces that act within and around cells to pull them into the right shape and location.

A structure called the extracellular matrix surrounds cells and provides them with support; it can also guide cell movements. It is not clear whether the extracellular matrix plays only a passive role or a more active, instructive role in shaping organs, in part, because it is difficult to measure the physical forces within densely packed cells.

The ovaries of the fruit fly Drosophila melanogaster provide a simple system in which to study how organs take their shape. Crest et al. developed a method to measure forces in the fly ovary as it changes from being an initially spherical group of cells to its final elongated tube shape. The results revealed that, during this process, the extracellular matrix becomes gradually stiffer from one end of the ovary to the other. This change is the main factor responsible for the cell rearrangements that shape the developing organ.

This work reveals that, along with providing structural support to cells, the mechanical properties of the matrix also actively guide how organs form. In the future, these findings may aid efforts to grow organs in a laboratory and to regenerate organs in human patients.