Intercellular Tension Negatively Regulates Angiogenic Sprouting of Endothelial Tip Cells via Notch1‐Dll4 Signaling

Abstract

Mechanical force plays pivotal roles in vascular development during tissue growth and regeneration. Nevertheless, the process by which mechanical force controls the vascular architecture remains poorly understood. Using a systems bioengineering approach, it is shown that intercellular tension negatively regulates tip cell formation via Notch1‐Dll4 signaling in mouse retinal angiogenesis in vivo, sprouting embryoid bodies, and human endothelial cell networks in vitro. Reducing the intercellular tension pharmacologically by a Rho‐associated protein kinase inhibitor or physically by single cell photothermal ablation of the capillary networks promotes the expression of Dll4, enhances angiogenic sprouting of tip cells, and increases the vascular density. Computational biomechanics, RNA interference, and single cell gene expression analysis reveal that a reduction of intercellular tension attenuates the inhibitory effect of Notch signaling on tip cell formation and induces angiogenic sprouting. Taken together, the results reveal a mechanoregulation scheme for the control of vascular architecture by modulating angiogenic tip cell formation via Notch1‐Dll4 signaling.

Linseed hydrogel-mediated green synthesis of silver nanoparticles for antimicrobial and wound-dressing applications

“…AgNO 3 (10,20, and 30 mmol) solution was mixed with LSH solution and progress of reaction was monitored at different temperatures (50, 75, and 100°C). This experiment was performed in dark to avoid any photochemical reaction.…”

“…A mixture of AgNO 3 (10,20, and 30 mmol) and LSH was exposed to diffused sunlight for 10 h. Mixture was air dried in dark in a petri dish to produce LSH thin films containing the embedded Ag NPs and stored in an air-tight container. After 6 months, dry film was dissolved in deionized water, and the resultant suspension was characterized through UV/Vis spectrophotometry.…”

“…Ag NPs were separated from LSH and AgNO 3 (10,20, and 30 mmol) solutions by centrifugation, and TEM image was recorded. TEM images confirmed the formation (Figure 5), respectively.…”

“…The more commonly used methods include chemical and photochemical reduction, 17,18 electrochemical method, 19 and laser ablation. 20,21 Use of chemical reduction method for synthesis of Ag NPs involves environmentally hostile reducing agents, 22,23 toxic solvents, 24 and nonbiodegradable/synthetic…”

Mechanical Regulation of Microvascular Angiogenesis

“…Many of these individual processes are known to be responsive to mechanical stimuli. For example, key molecular regulators of tip cell selection (10) have recently been identified as mechanosensitive (11,12), and expression and secretion of proteases that are involved in angiogenesis are also mechanosensitive (13,14). Collective cell migration requires the binding and release of ECM by adhesion molecules such as integrins (15), which act as important mediators of ECM-cell mechanotransduction (16).…”