Publications

BackgroundCollective migration is the coordinated movement of a group of cells-a fundamental process in health and disease. Many models have been developed to study the molecular and physical mechanisms of collective migration. However, the aim of this study is to engineer a flexible in vitro framework that allows for mechanobiological quantification of the separate and combined contributions of individual cell mechanics to the directed migration of a collective. We utilised this framework to understand the role of juxtacrine Notch signalling during collective endothelial migration-an essential process during the formation of new blood vessels (known as angiogenesis).ResultsThis framework enables users to perform high spatiotemporal analysis of migrative behaviour, cell-matrix traction forces, and intercellular forces in different microenvironments. With this framework, we show that Notch inhibited collectives adopt a distinct regime of directed collective migration. Whereas the directionality of migration, traction forces and intercellular forces are not affected by Notch inhibition, we observed spatiotemporal differences in migration speed, traction force magnitude and normal and shear stresses within Notch-inhibited collectives.ConclusionsThe in vitro framework is a powerful approach for dissecting the mechanisms of collective migration. With this framework, we show that a potential link exists between the juxtacrine signalling of Notch and an increased mechanical cohesiveness among collective cells.

JTD Keywords: Angiogenesis, Cell-cell dynamics, Cell-matrix dynamics, Collective endothelial migration, Dynamics, Forces, In vitro framework, Juxtacrine notch signalling, Migration kinematics, Morphogenesis, Organization

Cells are sensitive to the physical properties of their microenvironment and transduce them into biochemical cues that trigger gene expression and alter cell behavior. Numerous proteins, including integrins, are involved in these mechanotransductive events. Here, a novel role for the boron transporter NaBC1 is identified as a mechanotransducer. It is demonstrated that soluble boron ions activate NaBC1 to enhance cell adhesion and intracellular tension in C2C12 myoblasts seeded on fibronectin-functionalized polyacrylamide (PAAm) hydrogels. Retrograde actin flow and traction forces exerted by these cells are significantly increased in vitro in response to both increased boron concentration and hydrogel stiffness. These effects are fibronectin and NaBC1-mediated as they are abrogated in hydrogels coated with laminin-111 in place of fibronectin and in esiRNA NaBC1-silenced cells. These findings thus demonstrate that NaBC1 controls boron homeostasis and also functions as a mechanosensor.

JTD Keywords: Activation, Animals, Beta-1-integrin, Biomaterials, Boron, Cell adhesion, Cell line, Cell-matrix, Differentiation, Fibronectins, Focal adhesion kinase, Growth, Hydrogels, Integrins, Mechanobiology, Mechanotransduction, Mechanotransduction, cellular, Mediated adhesion, Mice, Muscle cells, Myoblasts, Nabc1, Skeletal-muscle, Stiffnes, Tissue engineerin, Tissue engineering