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in Vivo
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Katie M. Kilgour, Brendan L. Turner, Augustus Adams, Stefano Menegatti, Michael A. Daniele
Both angiogenetic mechanisms are controlled by growth factors, their receptors, and inhibitors. Chief among them is the family of vascular endothelial growth factors (VEGF), which comprises the four subclasses VEGF-A, VEGF-B, VEGF-C, and VEGF-D, and their receptors VEGFR1, VEGFR2, and VEGFR3 (Pandey et al., 2018). In particular, the VEGF-A/VEGFR2 signalling pair regulates most of the interactions involved in angiogenesis (Pandey et al., 2018). Upon binding VEGF-A, the VEGFR2 receptor activates the pathways (Akt and MAPK) that regulate metabolic, proliferative, and growth processes of endothelial cells resulting in angiogenesis (Pandey et al., 2018); concurrently, it triggers the production of nitric oxide, which enhances vascular permeability by vasodilation and lowers the blood pressure (Pandey et al., 2018). Other proteins involved in endothelial cell growth and migration are angiogenin, epidermal growth factor (EGF), oestrogen, interleukin 8 (IL-8), prostaglandins E1 and E2, and tissue necrotic factor α (TNF-α) (Barnabas, Wang, & Gao, 2013; Harada et al., 1994; Montrucchio et al., 1994; Semino, Kamm, & Lauffenburger, 2006; Shi & Wei, 2016). These actors form the biomolecular core of the processes of stem cell differentiation into endothelial cells and regulate their adhesion, migration, and proliferation, which collectively contribute to angiogenesis. In vivo, the cell-surrounding ECM comprises a variety of structural (e.g., collagen, laminin, and fibronectin (FN) (Wang & Borenstein, 2017) and signalling proteins (e.g., cytokines and growth factors (Wang & Borenstein, 2017)), as well as complex topological features (e.g., ports, ridges, and fibres), which cooperatively guide the activity and the motion of cells via chemotaxis, haptotaxis, and mechanotaxis (Nelson et al., 1996).
On the importance of substrate deformations for cell migration
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2019
A. Gagnieu, G. Chagnon, Y. Chemisky, A. Stephanou, A. Chauvière
Cell migration is essential for many biological processes such as tissue morphogenesis, wound healing or metastatic invasion in cancer. It is a complex and highly regulated phenomenon closely guided and fine-tuned by both chemical and mechanical cues. Whereas chemoattraction has been extensively studied, the mechanical influence remains to be fully elucidated. Although cell sensitivity to the substrate rigidity is known under the term durotaxis (Marzban et al. 2018) and substrate anisotropy is known to influence cellular organization (Checa et al. 2015) much less is known about cell sensitivity to environmental stresses and strains. This paper proposes to specifically focus on the cell sensitivity to substrate deformations during migration. Those are assumed to play a role in long-range cell-cell interactions (Han et al. 2018) by which a cell deforms the substrate (Tanimoto and Sano 2014) and influences the orientation of migration of other cells in its neighbourhood. This form of mechanotaxis (to which we will refer as strain mechanosensing) could in particular explain how cells migrate towards each other to form vascular loops during angiogenesis when chemotaxis is ruled out.