Integrin α5β1 nano-presentation regulates collective keratinocyte migration independent of substrate rigidity

Abstract

Nanometer-scale properties of the extracellular matrix influence many biological processes, including cell motility. While much information is available for single cell migration, to date, no knowledge exists on how the nanoscale presentation of extracellular matrix receptors influences collective cell migration. In wound healing, basal keratinocytes collectively migrate on a fibronectin-rich provisional basement membrane to re-epithelialize the injured skin. Among other receptors, the fibronectin receptor integrin α5β1 plays a pivotal role in this process. Using a highly specific integrin α5β1 peptidomimetic combined with nanopatterned hydrogels, we show that keratinocyte sheets regulate their migration ability at an optimal integrin α5β1 nanospacing. This efficiency relies on the effective propagation of stresses within the cell monolayer independent of substrate stiffness. For the first time, this work highlights the importance of extracellular matrix receptor nanoscale organization required for efficient tissue regeneration.

Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

“…Traction force and monolayer stress microscopy. Traction force quantification and monolayer stress calculations were performed as previously described (Di Russo et al, 2021;Vishwakarma et al, 2018).…”

“…Traction forces were calculated from these vectors using the Fourier transform traction cytometry plugin (FTTC) of Fiji (National Institutes of Health, USA). Next, average normal stress vectors were calculated using the traction force information using a force balance algorithm in MATLAB (MathWorks) as formulated elsewhere (Di Russo et al, 2021;Vishwakarma et al, 2018). For each measured sample, the average cell height was calculated using a live actin staining (SirActin, Spirochrome) to correctly input the force balance algorithm.…”

“…Overall monolayer traction force modulates RPE functionality Epithelial contractility levels have been shown to directly influence tissue functionality and reactivity (Vishwakarma et al, 2018;Di Russo et al, 2021;Park et al, 2015;Malinverno et al, 2017;Palamidessi et al, 2019;Balcioglu et al, 2020;Mongera et al, 2018;Pérez-González et al, 2021). Thus, we asked ourselves if the efficiency of RPE to phagocyte POS is generally affected by the level of monolayer traction forces independently of the biochemical nature of ECM adhesion, i.e., laminin isoforms or density.…”

Integrins regulation of wound healing processes: insights for chronic skin wound therapeutics

“…By Figdraw. Mediating VEGF-driven angiogenesis, negative feedback regulation of collagen synthesis in FBL (Senger and Davis, 2011;Gardner et al, 1999;Senger et al, 1997) a 2 b 1 Laminin, collagen Platelets, KC, EC and FBL Mediates KC migration and VEGF-driven angiogenesis (Senger et al, 1997;Grenache et al, 2007) a 3 b 1 Laminin, platelet-reactive protein KC、EC and FBL Regulation of KC migration during re-epithelialization (Margadant et al, 2009), control of angiogenesis and TGF-b1-mediated responses (da Silva et al, 2010) a 4 b 1 Thrombospondin, fibronectin, bone bridge protein, ADAM, EDA, VCAM, etc (Huhtala et al, 1995;Shinde et al, 2015;Abonia et al, 2006) Leukocytes, FBL, and EC Regulation of FBL proliferation and TGF-b1 processing (Shinde et al, 2015) a 5 b 1 Fibronectin, bone bridging protein, profibronectin, ADAM, CCN, etc (Huhtala et al, 1995;Lau, 2016) Platelets, KCs, ECs, FBLs Promote KC migration (Di Russo et al, 2021), etc.…”