Multiscale modeling of form and function.
Topobiology posits that morphogenesis is driven by differential adhesive interactions among heterogeneous cell populations. This paradigm has been revised to include force-dependent molecular switches, cell and tissue tension, and reciprocal interactions with the microenvironment. It is now appreciated that tissue development is executed through conserved decision-making modules that operate on multiple length scales from the molecular and subcellular level through to the cell and tissue level and that these regulatory mechanisms specify cell and tissue fate by modifying the context of cellular signaling and gene expression. Here, we discuss the origin of these decision-making modules and illustrate how emergent properties of adhesion-directed multicellular structures sculpt the tissue, promote its functionality, and maintain its homeostasis through spatial segregation and organization of anchored proteins and secreted factors and through emergent properties of tissues, including tension fields and energy optimization.
Engler
Adam J
AJ
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Humbert
Patrick O
PO
Wehrle-Haller
Bernhard
B
Weaver
Valerie M
VM
D000818:Animals; D005075:Biological Evolution; D002448:Cell Adhesion / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D002450:Cell Communication; D005109:Extracellular Matrix / Q000502:physiology*; D005838:Genotype; D006706:Homeostasis; D009024:Morphogenesis / Q000502:physiology*; D010641:Phenotype; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D011506:Proteins