Force inference predicts local and tissue-scale stress patterns in epithelia
Preprint posted on December 04, 2018 https://www.biorxiv.org/content/early/2018/12/04/475012
Embryo morphogenesis is inherently a mechanical process, where tissues fold, bend, loop and involute to reach their final geometries. In this regard, several techniques such as micropipette aspiration, magnetic tweezers and droplet injection have been developed in the last few years to probe the mechanics of epithelial tissues1. However, these techniques are generally invasive to the sample being investigated and are laborious to perform. There is an urgent need therefore to develop non-invasive methodologies to study tissue mechanics. The force inference method provides a good alternative to obtain relative estimates of stress distribution in a tissue in a non-invasive fashion.
The force inference method2 exploits the idea that at mechanical equilibrium, cell shapes are determined by a balance of contact forces between cells. Therefore, if cell shapes can be precisely determined by imaging followed by image segmentation, this method can be used for inferring relative tensions in a tissue. In the highlighted manuscript, the authors validate the force inference method numerically as well as experimentally by performing laser ablation in Drosophila tissues. They demonstrate the robustness of the force inference methodology in predicting stress patterns from single cell to tissue length scales.
The authors first validated the force inference method, by generating in silico tissues using the Surface Evolver software. A classical vertex model was used to generate a user defined surface, where tensions at the edges of cells and pressures in cells were assigned a pre-determined value. Based on these values, the software then performs energy minimization of the surface to yield a final geometry. From the final geometry, cell shapes were determined following which the force inference method was used to infer forces in the energy minimized surface. The authors find an excellent agreement between the pre-determined tension/pressure maps and the distribution of forces determined by the force inference method.
The authors then proceed to compare the force inference method with laser ablation experiments performed in three different Drosophila tissues at different length scales. Single junctional tension was probed in the pupal notum, changes in tension across a small group of cells was analyzed in the ommatidia (four cone cells are present in a single ommatidium) and large-scale tension in a tissue across hundreds of cells was evaluated in the germband. For the ommatidia and germband case studies, mutant conditions were also tested. In each case, laser ablation was performed and the associated recoil velocity upon ablation was measured. The recoil velocity is proportional to the tension in the region of interest prior to the ablation. In addition, the force inference method was used to infer tension in the three tissues. The inferred tension and measured recoil velocity were highly correlated in each of the three cases suggesting that the force inference method provides robust relative estimates of stress patterns in a developing tissue.
Why I chose this preprint?
The biggest advantage of the force inference method is that it is non-invasive. It still relies on various assumptions in the different models used for force inference. However, it provides a good complementary approach to invasive methodologies and allows researchers to infer forces in hard-to-access tissues that are deep inside embryos. Moreover, the methodology allows force inference across different length scales – from cell level dynamics to tissue-scale morphogenesis.
- A pre-requisite for using the force inference method involves precise segmentation of the tissue of interest. The tissues chosen in this article are relatively easy to segment given the high contrast of the fluorescence signal. How should one proceed with using the force inference method for tissues where segmentation is noisy and error-prone?
- A major assumption in the method that allows for inferring forces is that tissues are at mechanical equilibrium. However, this is not the case in many contexts of tissue morphogenesis, where cells undergo dynamic shape changes. What criteria can be used to determine when not to use the force inference method?
- Sugimura K, Lenne P-F and Graner F, Measuring forces and stresses in situ in living tissues, Development, 2016.
- Ishihara S and Sugimura K, Bayesian inference of force dynamics during morphogenesis, Journal of Theoretical Biology, 2012.
Posted on: 17th January 2019Read preprint
Also in the biophysics category:
Single molecule mechanics resolves the earliest events in force generation by cardiac myosin
|Selected by||Alyson Smith|
Octopi: Open configurable high-throughput imaging platform for infectious disease diagnosis in the field
|Selected by||Mariana De Niz|
A unified role for membrane-cortex detachment during cell protrusion initiation
|Selected by||Martim Dias Gomes|
Also in the developmental biology category:
Cyp26b1 is required for proper airway epithelial differentiation during lung development
|Selected by||Julio Sainz de Aja|
Modulation of β-catenin levels is critical for cranial neural crest patterning and dispersal into first pharyngeal arch
|Selected by||Sruthi Balakrishnan|
Arl13b regulates Sonic Hedgehog signaling from outside primary cilia
|Selected by||Alex Eve|
preListsbiophysics category:in the
Also in the developmental biology category:
SDB 78th Annual Meeting 2019
A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.
|List by||Alex Eve|
Lung Disease and Regeneration
This preprint list compiles highlights from the field of lung biology.
|List by||Rob Hynds|
Young Embryologist Network Conference 2019
Preprints presented at the Young Embryologist Network 2019 conference, 13 May, The Francis Crick Institute, London
|List by||Alex Eve|
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
|List by||Alexa Sadier|
BSCB/BSDB Annual Meeting 2019
Preprints presented at the BSCB/BSDB Annual Meeting 2019
|List by||Gautam Dey|
A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.
|List by||Shikha Nayar|