Continuous Dynamic Modeling of Regulated Cell Adhesion: Sorting, Intercalation, and Involution

dc.contributor.authorKo, Jason M.
dc.contributor.authorLobo, Daniel
dc.date.accessioned2020-07-28T19:05:25Z
dc.date.available2020-07-28T19:05:25Z
dc.date.issued2019-10-31
dc.description.abstractCell-cell adhesion is essential for tissue growth and multicellular pattern formation and crucial for the cellular dynamics during embryogenesis and cancer progression. Understanding the dynamical gene regulation of cell adhesion molecules (CAMs) responsible for the emerging spatial tissue behaviors is a current challenge because of the complexity of these nonlinear interactions and feedback loops at different levels of abstraction—from genetic regulation to whole-organism shape formation. To extend our understanding of cell and tissue behaviors due to the regulation of adhesion molecules, here we present a novel, to our knowledge, model for the spatial dynamics of cellular patterning, growth, and shape formation due to the differential expression of CAMs and their regulation. Capturing the dynamic interplay between genetic regulation, CAM expression, and differential cell adhesion, the proposed continuous model can explain the complex and emergent spatial behaviors of cell populations that change their adhesion properties dynamically because of inter- and intracellular genetic regulation. This approach can demonstrate the mechanisms responsible for classical cell-sorting behaviors, cell intercalation in proliferating populations, and the involution of germ layer cells induced by a diffusing morphogen during gastrulation. The model makes predictions on the physical parameters controlling the amplitude and wavelength of a cellular intercalation interface, as well as the crucial role of N-cadherin regulation for the involution and migration of cells beyond the gradient of the morphogen Nodal during zebrafish gastrulation. Integrating the emergent spatial tissue behaviors with the regulation of genes responsible for essential cellular properties such as adhesion will pave the way toward understanding the genetic regulation of large-scale complex patterns and shapes formation in developmental, regenerative, and cancer biology.en_US
dc.description.sponsorshipWe thank Bradford Peercy for critical comments on the article and the members of the Lobo Lab for helpful discussions. This work was supported by the National Science Foundation (NSF) under grant IIS-1566077. Computations used the UMBC High Performance Computing Facility (HPCF) supported by the NSF MRI program grants OAC-1726023, CNS-0821258, and CNS-1228778, the SCREMS program grant DMS-0821311, and UMBC.en_US
dc.description.urihttps://www.sciencedirect.com/science/article/abs/pii/S0006349519308823en_US
dc.format.extent30 pagesen_US
dc.genrejournal articles preprintsen_US
dc.identifierdoi:10.13016/m2ox8y-uzyu
dc.identifier.citationJason M. Ko and Daniel Lobo, Continuous Dynamic Modeling of Regulated Cell Adhesion: Sorting, Intercalation, and Involution, Biophysical Journal Volume 117, Issue 11, Pages 2166-2179(2019), https://doi.org/10.1016/j.bpj.2019.10.032en_US
dc.identifier.urihttps://doi.org/10.1016/j.bpj.2019.10.032
dc.identifier.urihttp://hdl.handle.net/11603/19262
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Biological Sciences Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.relation.ispartofUMBC Student Collection
dc.relation.ispartofUMBC Computer Science and Electrical Engineering Department
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rights© 2019 Biophysical Society
dc.subjectUMBC High Performance Computing Facility (HPCF)
dc.titleContinuous Dynamic Modeling of Regulated Cell Adhesion: Sorting, Intercalation, and Involutionen_US
dc.typeTexten_US

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
582429v1.full.pdf
Size:
8.53 MB
Format:
Adobe Portable Document Format
Description:

License bundle

Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.56 KB
Format:
Item-specific license agreed upon to submission
Description: