Tissue Eng Lecture_102413

Thus in our calculation o the total number of vegfr1

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Unformatted text preview: 11,200 (50)), an instantaneous VEGF-recept internalization rate of 4.3 3 10À4 per second, and FIGURE 2 The geometry of the initial domain. An EC bud (dark gray) the molecular weight for VEGF165 (7,49). The v protrudes into the domain from the parent blood vessel on the left; an given in Table 1. Receptor binding occurs very ra avascular tumor resides outside the domain on the right-hand side and pared to the timescale of endothelial cell migrati supplies VEGF to the stroma. The space between represents the stroma and liferation. Thus, we assume that an endothelial c is composed of extracellular matrix fibers (light gray), tissue-specific cells (black), and interstitial fluid (gray). binds an amount of VEGF equal to the lesser o our results with both planar experimental models (e.g., (32,36,47) and other two-dimensional computational models (41,43,45). Our model has the flexibility to examine capillary sprout development at different length scales. The Computational model of elongation and branching Biophysical Journal 92(9 32 cellular funct differences in sprout morphology. Fig. 5 shows the resulting also move ch sprouts when proliferation occurred at the base (top inset) Computational model of) of longation also shows the tension increa e the sprout. Fig. 5 and branching and at the tip (lower inset of the speeds relationship between the proximity of the proliferating reThis rate repr in Experimen speed observe view that pro competing fo coordination icant effect on does not rule regions may e Stroma com mechanism and anasto FIGURE 5 The relationship between the average rate of sprout extension As shown in branching str branching oc and molecula probabilistic simulated33 sp Computational model of elongation and branching 3116 Bauer et al. FIGURE 6 Numerical simulations ruling out the possibility that branching is induced solely by the tessellated structure of the stroma. For an identical 34 Angiogenesis steps: Tubulogenesis, lumen formation, anastomosis In order to be functional and carry blood, a sprouting capillary must: - Connect with another vessel (anastomose) Form a lumen (tubulogenesis) This part of angiogenesis remains the least understood, Lumen formation involves 35 Angiogenesis steps: Development 138 (21) Tubulogenesis, lumen formation, anastomosis A Intracellular vacuole coalescence Key C Lumenal repulsion B Intercellular vacuole exocytosis Tip cell Vacuole CD34-sialomucin Stalk cell VE-cadherin Fig. 3. M outgro Endothe intracel other an (B) Inter by prod intercel intercel (lumena initial ap sialomu negativ repulsio thereby membra lumen i (not sho Junction relocalisation Repulsion Gruedens and Gerhardt. Development. 2011 36 Computational model simulates anastomosis Bentley, Mariggi, Gerhardt, and Bates. PLoS Comput Biol. 2009 37 Computational model of anastomosis Computational methods: agent-based model - The cell agent is comprised of smaller agents (cell membrane) connected by springs to confer tension - Cell membrane agents respond to changes in their local environment - Agents contain receptors and ligands, determined based on their gene regulatory network - Springs follow Hooke’s Law 38 39 40 Computational model of anastomosis 41 Computational model of anastomosis 42 Angiogenesis steps: Stabilization and regression The final phase of angiogenesis is vessel maturation Pericytes stabilize and prevent regression • • • Prevent vascular leakage Regulate proliferation and migration Produce basement membrane Contradicting experimental data • • Pericyte recruitment marks end of vessel plasticity In tumors, pericyte coverage does not protect from regression 43 Angiog...
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