Modeling branching morphogenesis using materials with programmable mechanical instabilities

Abstract

The architectural features of branching morphogenesis demonstrate exquisite reproducibility among various organs and species despite the unique functionality and biochemical differences of their microenvironment. The regulatory networks that drive branching morphogenesis employ cell-generated and passive mechanical forces, which integrate extracellular signals from the microenvironment into morphogenetic movements. Cell-generated forces function locally to remodel the extracellular matrix (ECM) and control interactions among neighboring cells. Passive mechanical forces are the product of in situ mechanical instabilities that trigger out-of-plane buckling and clefting deformations of adjacent tissues. Many of the molecular and physical signals that underlie buckling and clefting morphogenesis remain unclear and require new experimental strategies to be uncovered. Here, we highlight soft material systems that have been engineered to display programmable buckles and creases. Using synthetic materials to model physicochemical and spatiotemporal features of buckling and clefting morphogenesis might facilitate our understanding of the physical mechanisms that drive branching morphogenesis across different organs and species.

ERK-mediated Curvature Feedback Regulates Branching Morphogenesis in Lung Epithelial Tissue

“…The results presented in this study provide a better understanding of lung epithelial branching, in conjunction with previously determined theory-based mechanisms, based on mechanical and chemical aspects. From a mechanical viewpoint, it has been proposed that the spatial patterning of the isolated lung epithelium arises from the proliferation-induced physical instability of the epithelial layer, known as mechanical buckling 36 , in various developing epithelial tissues 1,37,38 . This purely mechanical model may explain the formation of an initial branching pattern, under the assumption that the epithelial tissue acts as an elastic layer, but may require the physical conditions under which mechanical buckling occurs.…”

3D Organisation of Cells in Pseudostratified Epithelia

“…Vertex models have been developed to specifically represent epithelia in 3D, but without resolving the complex irregular shapes of epithelial cells [64,[75][76][77]. In 2D, several vertex-based models with higher cell boundary resolution have been developed to enable more complex cell shapes [78][79][80][81][82], and to represent individual cell boundaries and the interstitial volume [83][84][85][86]. A recent hybrid version between a spheroid and a vertex model allows for a 3D vertex model with an intermediate vertex that enables a neighbour transition along the apical-basal axis [87].…”

Mechanical regulation of the early stages of angiogenesis

“…However, other possible approaches are also potentially promising. For instance, since mechanical properties of biological tissues have been shown to be associated with instabilities that determine morphogenesis [327][328][329], the notion that angiogenic sprouting can be viewed as an instability is certainly worth exploring. In this type of paradigm, different stimuli compete to either amplify or dampen the formation of sprouts [330], with stochasticity as a key player in the process [331].…”