Modulators of endothelial cell filopodia

DeLisser, Horace M.

doi:10.4161/cam.5.1.13575

Cited by 11 publications

(8 citation statements)

References 56 publications

(66 reference statements)

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“…The presence of these filopodia is key to form focal points of adhesion where cells can anchor and stabilize to promote migration and proliferation. This endothelial cell motility is a critical aspect of angiogenesis [64]. Finally, we found out a comparable average cell proliferation to previous studies for EC culture over biodegradable scaffolds [63,65].…”

Section: Discussionsupporting

confidence: 86%

Design and Characterization of a Fluidic Device for the Evaluation of SIS-Based Vascular Grafts

et al. 2020

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Currently available small diameter vascular conduits present several long-term limitations, which has prevented their full clinical implementation. Commercially available vascular grafts show no regenerative capabilities and eventually require surgical replacement; therefore, it is of great interest to develop alternative regenerative vascular grafts (RVG). Decellularized Small Intestinal Submucosa (SIS) is an attractive material for RVG, however, the evaluation of the performance of these grafts is challenging due to the absence of devices that mimic the conditions found in vivo. Thereby, the objective of this study is to design, manufacture and validate in silico and in vitro, a novel fluidic system for the evaluation of human umbilical vein endothelial cells (HUVECs) proliferation on SIS-based RVG under dynamical conditions. Our perfusion and rotational fluidic system was designed in Autodesk Inventor 2018. In silico Computational Fluid Dynamics (CFD) validation of the system was carried out using Ansys Fluent software from ANSYS, Inc for dynamical conditions of a pulsatile pressure function measured experimentally over a rigid wall model. Mechanical and biological parameters such as flow regime, pressure gradient, wall shear stress (WSS), sterility and indirect cell viability (MTT assay) were also evaluated. Cell adhesion was confirmed by SEM imaging. The fluid flow regime within the system remains laminar. The system maintained sterility and showed low cytotoxicity levels. HUVECs were successfully cultured on SIS-based RVG under both perfusion and rotation conditions. In silico analysis agreed well with our experimental and theoretical results, and with recent in vitro and in vivo reports for WSS. The system presented is a tool for evaluating RVG and represents an alternative to develop new methods and protocols for a more comprehensive study of regenerative cardiovascular devices.

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Section: Discussionsupporting

confidence: 86%

Design and Characterization of a Fluidic Device for the Evaluation of SIS-Based Vascular Grafts

et al. 2020

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“…Using beads as a tool to probe cell-ECM interactions allows the analysis of the deformation field throughout the entire ECM while minimally interfering with cell activities. This is based on (i) the average gap between two adjacent beads (nearly 14 μ m over a 227 × 105- μ m region in the image plane that best represented the sprout center) was sufficient to allow filopodia (routinely in a diameter ranging from 0.1 μ m to 0.3 μ m 24 25 ) to freely protrude and swerve within the bead-containing ECM and (ii) the change in ECM stiffness produced by the beads at the concentration used (i.e., 0.075 mg/ml) was negligible. The latter concurred with our previous studys finding that a 5% change in ECM stiffness was associated with the addition to the ECM of 0.1 mg/ml of beads of the same size as those used in the current study 26 .…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Characterization of Mechanical Interactions between Endothelial Cells and Extracellular Matrix during Angiogenic Sprouting

Herath

Wang

et al. 2016

Sci Rep

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We studied the three-dimensional cell-extracellular matrix interactions of endothelial cells that form multicellular structures called sprouts. We analyzed the data collected in-situ from angiogenic sprouting experiments and identified the differentiated interaction behavior exhibited by the tip and stalk cells. Moreover, our analysis of the tip cell lamellipodia revealed the diversity in their interaction behavior under certain conditions (e.g., when the heading of a sprout is switched approximately between the long-axis direction of two different lamellipodia). This study marks the first time that new characteristics of such interactions have been identified with shape changes in the sprouts and the associated rearrangements of collagen fibers. Clear illustrations of such changes are depicted in three-dimensional views.

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“…Cytoplasmic slender projections, for example filopodia, were suggested to function as antennae to sense the biochemical and biophysical cues given by the surrounding substratum, for example ECM, in turn guiding cellular locomotion [4]. For endothelial cells in particular, filopodia were identified at the tip cell, which leads sprouting vessels during angiogenesis [5,6]. Owing to the key role of filopodia associated with angiogenesis, extensive studies have been performed to identify the signalling pathways and molecular regulators of endothelial filopodia [5,7].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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.

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Modulators of endothelial cell filopodia

Cited by 11 publications

References 56 publications

Design and Characterization of a Fluidic Device for the Evaluation of SIS-Based Vascular Grafts

Design and Characterization of a Fluidic Device for the Evaluation of SIS-Based Vascular Grafts

Three-Dimensional Characterization of Mechanical Interactions between Endothelial Cells and Extracellular Matrix during Angiogenic Sprouting

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

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