The temporal basis of angiogenesis

Abstract

The process of new blood vessel growth (angiogenesis) is highly dynamic, involving complex coordination of multiple cell types. Though the process must carefully unfold over time to generate functional, well-adapted branching networks, we seldom hear about the time-based properties of angiogenesis, despite timing being central to other areas of biology. Here, we present a novel, time-based formulation of endothelial cell behaviour during angiogenesis and discuss a flurry of our recent, integrated in silico/in vivo studies, put in context to the wider literature, which demonstrate that tissue conditions can locally adapt the timing of collective cell behaviours/decisions to grow different vascular network architectures. A growing array of seemingly unrelated ‘temporal regulators’ have recently been uncovered, including tissue derived factors (e.g. semaphorins or the high levels of VEGF found in cancer) and cellular processes (e.g. asymmetric cell division or filopodia extension) that act to alter the speed of cellular decisions to migrate. We will argue that ‘temporal adaptation’ provides a novel account of organ/disease-specific vascular morphology and reveals ‘timing’ as a new target for therapeutics. We therefore propose and explain a conceptual shift towards a ‘temporal adaptation’ perspective in vascular biology, and indeed other areas of biology where timing remains elusive.This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’.

Fast quantitative time lapse displacement imaging of endothelial cell invasion

“…All together these results reveal that neighbouring sprouts invade collectively (within 24 hours) but in a non-synchronous, highly dynamic fashion; which is in line with current studies reporting that asynchronous selection of tip cells-regulated by asynchronous individual cell protein dynamics-is required for normal network formation [64][65][66].…”

Angiogenesis in Tissue Engineering: As Nature Intended?

“…Angiogenesis is a dynamic process where a series of events progress following a precisely timed schedule (Bentley and Chakravartula, 2017). At the single cell level, mechanical and chemical sensing drive the internal signaling response and consequent actions (proliferation, migration, and differentiation).…”

Positive-feedback defines the timing and robustness of angiogenesis

“…However, we have little-to-no understanding of the underlying temporal features of these decision-making processes. Indeed, lateral inhibition is considered relatively slow, taking upwards of 6 h to complete multiple cycles of gene expression needed to amplify initially small differences in input signal [14,[16][17][18][19], which is seemingly incompatible with the rapid dynamic changes in EC state, identity and behavior observed in angiogenesis [20,21].…”