title: Substrate adhesion regulates sealing zone architecture and dynamics in cultured osteoclasts.
abstract: The bone-degrading activity of osteoclasts depends on the formation of a cytoskeletal-adhesive super-structure known as the sealing zone (SZ). The SZ is a dynamic structure, consisting of a condensed array of podosomes, the elementary adhesion-mediating structures of osteoclasts, interconnected by F-actin filaments. The molecular composition and structure of the SZ were extensively investigated, yet despite its major importance for bone formation and remodelling, the mechanisms underlying its assembly and dynamics are still poorly understood. Here we determine the relations between matrix adhesiveness and the formation, stability and expansion of the SZ. By growing differentiated osteoclasts on micro-patterned glass substrates, where adhesive areas are separated by non-adhesive PLL-g-PEG barriers, we show that SZ growth and fusion strictly depend on the continuity of substrate adhesiveness, at the micrometer scale. We present a possible model for the role of mechanical forces in SZ formation and reorganization, inspired by the current data.
authors.affiliation: Laboratory for Surface Science and Technology, Department of Materials, ETH Zurich, Zurich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Anderegg
authors.forename: Dafna
authors.initials: D
authors.lastname: Geblinger
authors.forename: Peter
authors.initials: P
authors.lastname: Horvath
authors.forename: Mirren
authors.initials: M
authors.lastname: Charnley
authors.forename: Marcus
authors.initials: M
authors.lastname: Textor
authors.forename: Lia
authors.initials: L
authors.lastname: Addadi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Geiger
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry; D000818:Animals; D001842:Bone and Bones / Q000473:pathology*; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000737:chemistry; D005898:Glass; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D018715:Microscopy, Video / Q000379:methods; D010010:Osteoclasts / Q000166:cytology*; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000031:analogs & derivatives / Q000737:chemistry; D013314:Stress, Mechanical; D013499:Surface Properties; D016596:Vinculin / Q000737:chemistry; D019096:Vitronectin / Q000737:chemistry
chemical_list: D019096:Vitronectin; C443714:polylysine-graft-(poly(ethylene glycol)); D016596:Vinculin; D011107:Polylysine; D011092:Polyethylene Glycols