Dynamics of filopodium-like protrusion and endothelial cellular motility on one-dimensional extracellular matrix fibrils

Abstract

Endothelial filopodia play key roles in guiding the tubular sprouting during angiogenesis. However, their dynamic morphological characteristics, with the associated implications in cell motility, have been subjected to limited investigations. In this work, the interaction between endothelial cells and extracellular matrix fibrils was recapitulated in vitro, where a specific focus was paid to derive the key morphological parameters to define the dynamics of filopodium-like protrusion during cell motility. Based on one-dimensional gelatin fibrils patterned by near-field electrospinning (NFES), we study the response of endothelial cells (EA.hy926) under normal culture or ROCK inhibition. It is shown that the behaviour of temporal protrusion length versus cell motility can be divided into distinct modes. Persistent migration was found to be one of the modes which permitted cell displacement for over 300 mm at a speed of approximately 1 mm min 21. ROCK inhibition resulted in abnormally long protrusions and diminished the persistent migration, but dramatically increased the speeds of protrusion extension and retraction. Finally, we also report the breakage of protrusion during cell motility, and examine its phenotypic behaviours.

Protrusive waves guide 3D cell migration along nanofibers

“…Similar actin-based waves have been observed during neuron extension and axonogenesis in vivo ( Edmondson and Hatten, 1987 ; Flynn et al, 2009 ; Govek et al, 2011 ). By observing these fin-like protrusions at a high spatio-temporal resolution, we were able to determine that these fins guide cell migration along fibers but also analyze their dynamics, a finding that has not been reported in previous studies ( Lee et al, 2013 ; Sharma et al, 2013 ; Xue et al, 2014 ; Higgins et al, 2015 ). Importantly, our study demonstrated that these waves of fin-like protrusions are exhibited and used by a variety of cell types, including endothelial, glioma, and fibroblast cell lines (Table S1), suggesting that is a widely used mechanism for fibrillar migration.…”

Distinct roles for IκB kinases alpha and beta in regulating pulmonary endothelial angiogenic function during late lung development

“…Endothelial filopodia serve as antennae, detecting chemical and mechanical cues in the environment. Motility is directed by anchoring filopodial protrusions and subsequent retraction of the cell body, moving the cell forward . Further studies will need to explore whether the effect we observed in the VCAM depleted cells is secondary to decreases in soluble VCAM expression, or if cell surface VCAM has a previously unrecognized function in mediating appropriate sensing and anchoring of filopodia.…”

Architecture and migration of an epithelium on a cylindrical wire

“…The available surface is then too small to allow cells' lamellipodium to develop sufficient adhesions, leading to the unstable protrusions/retraction cycles (49,50). As it becomes denser, the whole monolayer then undergoes strong morphogenetic movements that eventually lead to cyst formation at the cone tips.…”