Podosomes in space

Macrophage-Dependent Trafficking and Remodeling of the Basement Membrane-Interstitial Matrix Interface

“…Instead, both human and mouse macrophages deployed the membrane-anchored MMP, MT1-MMP, as the dominant effector of basement membrane remodeling. Interestingly, in a manner similar to that observed during podosome-mediated proteolysis (Wiesner et al, 2013; Wiesner et al, 2014), MT1-MMP actively trafficked to invasive membrane protrusions as the macrophages penetrated the basement membrane. While we have not examined this exocytotic process in detail, MT1-MMP trafficking most likely involves the RabGTPase-microtubule system previously detailed by Linder and colleagues (Wiesner et al, 2013; Wiesner, Faix, Himmel, Bentzien, & Linder, 2010).…”

“…Y. Murray et al, 2013; Ogura, Bridgeman, & Malanchi, 2017; Starnes et al, 2014; Van Goethem et al, 2010; Werb, Bainton, & Jones, 1980). However, given increased appreciation that these constructs cannot recapitulate the more complex structure of the ECM in vivo , and that the composition and mechanical properties of the ECM can each affect cell function (Liu et al, 2015; Previtera & Sengupta, 2015; Wiesner et al, 2014), the utility of these systems for predicting macrophage function in vivo is subject to debate. For example, whereas basement membranes in vivo are type IV collagen-rich and mechanically rigid as a consequence of lysyl oxidase- and peroxidasin-mediated covalent crosslinks, in vitro constructs that rely on EHS carcinoma extracts (i.e., Matrigel) are alternatively enriched with laminin, mechanically soft and largely devoid of the critical type IV collagen crosslinks that define basement membrane structure (Halfter et al, 2015; Rowe & Weiss, 2008, 2009; Willis, Sabeh, Li, & Weiss, 2013).…”

“…To date, however, efforts to characterize human macrophage-ECM interactions have largely been confined to the use of artificial matrix constructs that lack the critical structural organization and mechanical properties that characterize the ECM in vivo (Cougoule et al, 2012; Halfter et al, 2015; Jevnikar et al, 2012; Daniel Hargbøl Madsen et al, 2017; Randles et al, 2017; Rowe & Weiss, 2008, 2009; Starnes et al, 2014; Van Goethem, Poincloux, Gauffre, Maridonneau-Parini, & Le Cabec, 2010; Wiesner, Le-Cabec, El Azzouzi, Maridonneau-Parini, & Linder, 2014). Hence, despite the fact that macrophages can mobilize a complex repertoire of proteolytic enzymes belonging to the aspartyl-, serine-, cysteine- and metallo-proteinase families, which, if any, of these systems participate in tissue remodeling and invasion remains undefined (Akkari et al, 2014; Nathan & Ding, 2010; Newby, 2016; Sevenich & Joyce, 2014; Vérollet et al, 2011).…”

Rapid 3D Extrusion of Synthetic Tumor Microenvironments

“…Inner channel periodicity does not affect cross‐linking or porosity in the bulk. Significant structural changes of the hydrogel fibers suggestive of remodeling is seen after 4 d culture with macrophages (Figure i) . We find that over 90% of encapsulated cells were viable within the first week of culture ( Figure c), with no significant changes in viability over 3 weeks.…”

Unraveling the Mechanobiology of the Immune System

“…Their primary role is to scan their niche environment, phagocytose cellular debris, support tissue regeneration, and guard against harmful pathogens. To support homeostasis in various parts of the body, macrophages have developed specific mechanisms that allow efficient migration . However, macrophage migration is not always desirable as macrophage infiltration can promote autoimmune diseases and aggravate neuroinflammation .…”