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Biology subjects

Kalcher, C.

Publications and source records attributed to Kalcher, C..

2 recordsLinked to original sources

SEM2: A computational framework to model multiscale mechanics with subcellular elements

Modeling multiscale mechanics in shape-shifting biological tissues in embryos, traditional, or engineered cell culture platforms (organoids, organs-on-chips) is both important and challenging. In fact, it is difficult to model relevant tissue-level structural changes mediated by discrete events at the cellular and subcellular levels, such as migration and proliferation. To accomplish this, we leveraged the subcellular element modeling (SEM) method, where ensembles of coarse-grained particles interacting via empirically defined potentials are used to model individual cells while preserving cell rheology. However, an explicit treatment of multiscale mechanics in SEM was missing. Here, we introduced SEM2, an extended version of the open-source software SEM++ and LAMMPS, enabling new analyses and visualization of particle-level stress and strain. We demonstrated various functionalities of SEM2 by simulating cell creep, migration, and proliferation in scenarios that recapitulate classical and engineered cell culture platforms. For every scenario, we highlight key mechanobiology that emerges spontaneously from particle interactions and discuss recent experimental evidence as qualitative validations of our simulations. The code for SEM2 is available on GitHub at https://github.com/Synthetic-Physiology-Lab/sem2.

bioengineering↗

Anti-fibrotic activity of an antimicrobial peptide in a Drosophila model.

Fibrotic lesions accompany several pathological conditions including tumors. We show that expression of a dominant-active form of the Ras oncogene in Drosophila salivary glands (SGs) leads to redistribution of components of the basement membrane (BM) and fibrotic lesions. Similar to several types of mammalian fibrosis, the disturbed BM attracts clot components including insect transglutaminase and phenoloxidase. SG epithelial cells show reduced apico-basal polarity accompanied by a loss of secretory activity. Both the fibrotic lesions and the reduced cell polarity are alleviated by ectopic expression of the antimicrobial peptide Drosomycin (Drs), which also restores secretory activity of the SGs. In addition to ECM components, both Drs and F-actin localize to fibrotic lesions.

immunology↗