Nano-topography sensing by osteoclasts.

doi:10.1242/JCS.060954

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Nano-topography sensing by osteoclasts.

Journal Article•DOI•

Nano-topography sensing by osteoclasts.

Dafna Geblinger¹, Lia Addadi¹, Benjamin Geiger¹•Institutions (1)

Weizmann Institute of Science¹

01 May 2010-Journal of Cell Science (The Company of Biologists Ltd)-Vol. 123, Iss: 10, pp 1503-1510

TL;DR: It was observed that steps or sub-micrometer cracks on the smooth surface stimulate local ring formation, raising the possibility that similar imperfections on bone surfaces may stimulate local osteoclast resorptive activity.

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Abstract: Bone resorption by osteoclasts depends on the assembly of a specialized, actin-rich adhesive ‘sealing zone’ that delimits the area designed for degradation. In this study, we show that the level of roughness of the underlying adhesive surface has a profound effect on the formation and stability of the sealing zone and the associated F-actin. As our primary model substrate, we use ‘smooth’ and ‘rough’ calcite crystals with average topography values of 12 nm and 530 nm, respectively. We show that the smooth surfaces induce the formation of small and unstable actin rings with a typical lifespan of ~8 minutes, whereas the sealing zones formed on the rough calcite surfaces are considerably larger, and remain stable for more than 6 hours. It was further observed that steps or sub-micrometer cracks on the smooth surface stimulate local ring formation, raising the possibility that similar imperfections on bone surfaces may stimulate local osteoclast resorptive activity. The mechanisms whereby the physical properties of the substrate influence osteoclast behavior and their involvement in osteoclast function are discussed.

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Journal Article•DOI•

Balancing forces: architectural control of mechanotransduction

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Christopher C. DuFort¹, Matthew J. Paszek¹, Valerie M. Weaver¹•Institutions (1)

University of California, San Francisco¹

01 May 2011-Nature Reviews Molecular Cell Biology

TL;DR: Sustained disruptions in tensional homeostasis can be caused by alterations in the extracellular matrix, allowing it to serve as a mechanically based memory-storage device that can perpetuate a disease or restore normal tissue behaviour.

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Abstract: All cells exist within the context of a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. These cues can be disrupted through perturbations to mechanotransduction, from the nanoscale-level to the tissue-level, which compromises tensional homeostasis to promote pathologies such as cardiovascular disease and cancer. The mechanisms of such perturbations suggest that a complex interplay exists between the extracellular microenvironment and cellular function. Furthermore, sustained disruptions in tensional homeostasis can be caused by alterations in the extracellular matrix, allowing it to serve as a mechanically based memory-storage device that can perpetuate a disease or restore normal tissue behaviour.

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875 citations

Cites background from "Nano-topography sensing by osteocla..."

...On a more specific level, the spatial presentation of ECM ligands, such as fibronectin, vitronectin, laminin and collagen, and the nanotopography of the ECM, control integrin organization, adhesion assembly, and signal transduction to direct cell behaviou...
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Journal Article•DOI•

Molecular Architecture and Function of Matrix Adhesions

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Benjamin Geiger¹, Kenneth M. Yamada²•Institutions (2)

Weizmann Institute of Science¹, National Institutes of Health²

01 May 2011-Cold Spring Harbor Perspectives in Biology

TL;DR: These cell adhesions play crucial roles in cell migration, proliferation, and determination of cell fate, and are mediated by membrane receptors such as the integrins, as well as many other components that comprise the adhesome.

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Abstract: Cell adhesions mediate important bidirectional interactions between cells and the extracellular matrix. They provide an interactive interface between the extracellular chemical and physical environment and the cellular scaffolding and signaling machinery. This dynamic, reciprocal regulation of intracellular processes and the matrix is mediated by membrane receptors such as the integrins, as well as many other components that comprise the adhesome. Adhesome constituents assemble themselves into different types of cell adhesion structures that vary in molecular complexity and change over time. These cell adhesions play crucial roles in cell migration, proliferation, and determination of cell fate.

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507 citations

Cites background from "Nano-topography sensing by osteocla..."

...Cells can also respond to the micro- or even nano-topography of a surface to which they adhere (Curtis and Wilkinson 1997; Cukierman et al. 2001; Geiger et al. 2001; Baharloo et al. 2005; Grossner-Schreiber et al. 2006; Vogel et al. 2006; Geblinger et al. 2010)....
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...They can assemble into large, belt-like superstructures, and are implicated in matrix-modulating activities (e.g., bone resorption by osteoclasts (Geblinger et al. 2010) and matrix invasion by a variety of cancer cells (Gimona et al. 2008)....
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...2006), regulating their dynamic properties (Geblinger et al. 2010), and modulating their signaling activity....
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...Cells can also respond to the micro-topography or even nano-topography of a surface to which they adhere (Curtis and Wilkinson 1997; Cukierman et al. 2001; Geiger et al. 2001; Baharloo et al. 2005; Grossner-Schreiber et al. 2006; Vogel et al. 2006; Geblinger et al. 2010)....
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...…surface features that are known to play a role in guiding the formation of matrix adhesions (Cukierman et al. 2001; Geiger et al. 2001; Baharloo et al. 2005; Grossner-Schreiber et al. 2006), regulating their dynamic properties (Geblinger et al. 2010) and modulating their signaling activity....
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Journal Article•DOI•

Nanotopographical Control of Stem Cell Differentiation

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Laura E. McNamara¹, Rebecca J. McMurray¹, Manus J.P. Biggs², Fahsai Kantawong¹, Richard O.C. Oreffo³, Matthew J. Dalby¹ - Show less +2 more•Institutions (3)

University of Glasgow¹, Columbia University², University of Southampton³

01 Jan 2010-Journal of Tissue Engineering

TL;DR: Nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal) stem cells.

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Abstract: Stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate determination would have tremendous potential for basic research and clinical therapy. Nanotopography provides a useful tool for guiding differentiation, as the features are more durable than surface chemistry and can be modified in size and shape to suit the desired application. In this paper, nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal) stem cells. To address the mechanistic basis underlying the topographical effects on stem cells, the likely contributions of indirect (biochemical signal-mediated) and direct (force-mediated) mechanotransduction are discussed. Data from proteomic research is also outlined in relation to topography-mediated fate determination, as this approach provides insight into the global molecular changes at the level of the functional effectors.

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349 citations

Cites background from "Nano-topography sensing by osteocla..."

...diverse cell types including fibroblasts [18, 22], osteoblasts [23], osteoclasts [24, 25], endothelial [15], smooth muscle [26], epithelial [27, 28], and epitenon cells [16]....
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Journal Article•DOI•

Degrading devices: invadosomes in proteolytic cell invasion.

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Stefan Linder, Christiane Wiesner, Mirko Himmel

10 Oct 2011-Annual Review of Cell and Developmental Biology

TL;DR: An overview of the field is provided, with special focus on current developments such as intracellular transport processes, ultrastructural analysis, the possible involvement of invadosomes in disease, and the tentative identification of invadoomes in 3D environments and in vivo.

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Abstract: Podosomes and invadopodia, collectively known as invadosomes, are cell-matrix contacts in a variety of cell types, such as monocytic cells or cancer cells, that have to cross tissue barriers. Both structures share an actin-rich core, which distinguishes them from other matrix contacts, and are regulated by a multitude of signaling pathways including RhoGTPases, kinases, actin-associated proteins, and microtubule-dependent transport. Invadosomes recruit and secrete proteinases and are thus able to lyse extracellular matrix components. They are therefore considered to be potential key structures in proteolytic cell invasion in both physiological and pathological settings. This review provides an overview of the field, with special focus on current developments such as intracellular transport processes, ultrastructural analysis, the possible involvement of invadosomes in disease, and the tentative identification of invadosomes in 3D environments and in vivo.

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346 citations

Journal Article•DOI•

Extracellular matrix networks in bone remodeling.

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Andrea I. Alford¹, Kenneth M. Kozloff¹, Kurt D. Hankenson²•Institutions (2)

University of Michigan¹, Michigan State University²

01 Aug 2015-The International Journal of Biochemistry & Cell Biology

TL;DR: This comprehensive review will focus on how networks of ECM proteins function to regulate osteoclast- and osteoblast-mediated bone remodeling and the clinical significance of these networks on normal bone and as they relate to pathologies of bone mass and geometry will be considered.

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223 citations

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Journal Article•DOI•

Adhesion-mediated mechanosensitivity: a time to experiment, and a time to theorize.

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Alexander D. Bershadsky¹, Michael M. Kozlov², Benjamin Geiger¹•Institutions (2)

Weizmann Institute of Science¹, Tel Aviv University²

01 Oct 2006-Current Opinion in Cell Biology

TL;DR: Experiments have been carried out that have started to uncover the major signaling pathways involved in the response of adhesion sites to force, and theoretical models have also been used to address the physical mechanisms underlying adhesion-mediated mechanosensing.

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401 citations

Journal Article•DOI•

Induction of cell polarization and migration by a gradient of nanoscale variations in adhesive ligand spacing.

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Marco Arnold¹, Vera C. Hirschfeld-Warneken¹, Theobald Lohmüller¹, Patrick Heil¹, Jacques Blümmel¹, Elisabetta Ada Cavalcanti-Adam¹, Mónica López-Garcia², Paul Walther², Horst Kessler², Benjamin Geiger², Joachim P. Spatz¹ - Show less +7 more•Institutions (2)

Max Planck Society¹, Weizmann Institute of Science²

18 Jun 2008-Nano Letters

TL;DR: It is shown that cells plated on surfaces that present a molecularly defined spacing gradient of an integrin RGD ligand can sense small but consistent differences in adhesive ligand spacing and induce cell polarization and initiate cell migration and signaling.

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Abstract: Cell interactions with adhesive surfaces play a vital role in the regulation of cell proliferation, viability, and differentiation, and affect multiple biological processes. Since cell adhesion depends mainly on the nature and density of the adhesive ligand molecules, spatial molecular patterning, which enables the modulation of adhesion receptor clustering, might affect both the structural and the signaling activities of the adhesive interaction. We herein show that cells plated on surfaces that present a molecularly defined spacing gradient of an integrin RGD ligand can sense small but consistent differences in adhesive ligand spacing of about 1 nm across the cell diameter, which is approximately 61 μm when the spacing includes 70 nm. Consequently, these positional cues induce cell polarization and initiate cell migration and signaling. We propose that differential positional clustering of the integrin transmembrane receptors is used by cells for exploring and interpreting their environment, at high spa...

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290 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...…Monchau et al., 2002; Redey et al., 1999; Roach et al., 2007; Shimizu et al., 1989), local density of the adhesive ligands (Arnold et al., 2004; Arnold et al., 2008; Hirschfeld-Warneken et al., 2008), and physical properties (Bershadsky et al., 2006a; Bershadsky et al., 2006b; Engler et al.,…...
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Journal Article•DOI•

The Architecture of the Adhesive Apparatus of Cultured Osteoclasts: From Podosome Formation to Sealing Zone Assembly

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Chen Luxenburg¹, Dafna Geblinger¹, Eugenia Klein¹, Karen L. Anderson², Dorit Hanein², Benny Geiger¹, Lia Addadi¹ - Show less +3 more•Institutions (2)

Weizmann Institute of Science¹, Sanford-Burnham Institute for Medical Research²

31 Jan 2007-PLOS ONE

TL;DR: The molecular architecture of the osteoclast resorptive apparatus is mapped from individual podosomes to the sealing zone, at an unprecedented resolution, forming a unique continuous functional structure connecting the cell to its extracellular milieu.

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Abstract: Background Osteoclasts are bone-degrading cells, which play a central role in physiological bone remodeling. Unbalanced osteoclast activity is largely responsible for pathological conditions such as osteoporosis. Osteoclasts develop specialized adhesion structures, the so-called podosomes, which subsequently undergo dramatic reorganization into sealing zones. These ring-like adhesion structures, which delimit the resorption site, effectively seal the cell to the substrate forming a diffusion barrier. The structural integrity of the sealing zone is essential for the cell ability to degrade bone, yet its structural organization is poorly understood. Principal Findings Combining high-resolution scanning electron microscopy with fluorescence microscopy performed on the same sample, we mapped the molecular architecture of the osteoclast resorptive apparatus from individual podosomes to the sealing zone, at an unprecedented resolution. Podosomes are composed of an actin-bundle core, flanked by a ring containing adhesion proteins connected to the core via dome-like radial actin fibers. The sealing zone, hallmark of bone-resorbing osteoclasts, consists of a dense array of podosomes communicating through a network of actin filaments, parallel to the substrate and anchored to the adhesive plaque domain via radial actin fibers. Significance The sealing zone of osteoclasts cultured on bone is made of structural units clearly related to individual podosomes. It differs from individual or clustered podosomes in the higher density and degree of inter-connectivity of its building blocks, thus forming a unique continuous functional structure connecting the cell to its extracellular milieu. Through this continuous structure, signals reporting on the substrate condition may be transmitted to the whole cell, modulating the cell response under physiological and pathological conditions.

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273 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...The architecture of the Jo ur na l o f C el l S ci en ce podosomes, and the manner in which they assemble into sealing zones, are similar on calcite, bone and glass (Geblinger et al., 2009; Luxenburg et al., 2007)....
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...The entire ring behaves as a single, complex network built of core units communicating with each other via the cytoskeleton, as well as with the substrate, through the podosomal adhesion plaque (Luxenburg et al., 2007)....
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...The basic architecture of individual podosomes, and their general tendency to interact with each other via interconnecting actin fibers and form ring-like superstructures, is an intrinsic property of osteoclasts (Geblinger et al., 2009; Luxenburg et al., 2007)....
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...To degrade bone, osteoclasts adhere to the bone surface via specialized, actin-rich adhesion sites known as podosomes, which assemble into a ring-shaped ‘sealing zone’ (Luxenburg et al., 2007; Vaananen and Horton, 1995)....
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Journal Article•DOI•

Nanometer surface roughness increases select osteoblast adhesion on carbon nanofiber compacts

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Rachel L. Price¹, Karen S. Ellison¹, Karen M. Haberstroh¹, Thomas J. Webster¹•Institutions (1)

Purdue University¹

01 Jul 2004-Journal of Biomedical Materials Research Part A

TL;DR: Due to a high degree of nanometer surface roughness, carbon fibers with nanometer dimensions may be optimal materials to selectively increase osteoblast adhesion necessary for successful orthopedic/dental implant applications.

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Abstract: Carbon nanofibers have exceptional theoretical mechanical properties (such as low weight-to-strength ratios) that, along with possessing nanoscale fiber dimensions similar to crystalline hydroxyapatite found in bone, suggest strong possibilities for use as an orthopedic/dental implant material. To determine, for the first time, cytocompatibility properties pertinent for bone prosthetic applications, osteoblast (bone-forming cells), fibroblast (cells contributing to callus formation and fibrous encapsulation events that result in implant loosening), chondrocyte (cartilage-forming cells), and smooth muscle cell (for comparison purposes) adhesion were determined on carbon nanofibers in the present in vitro study. Results provided evidence that, compared to conventional carbon fibers, nanometer dimension carbon fibers promoted select osteoblast adhesion. Moreover, adhesion of other cells was not influenced by carbon fiber dimensions. In fact, smooth muscle cell, fibroblast, and chondrocyte adhesion decreased with an increase in either carbon nanofiber surface energy or simultaneous change in carbon nanofiber chemistry. To determine properties that selectively enhanced osteoblast adhesion, similar cell adhesion assays were performed on polymer (specifically, poly-lactic-co-glycolic; PLGA) casts of carbon fiber compacts previously tested. Compared to PLGA casts of conventional carbon fibers, results provided the first evidence of enhanced select osteoblast adhesion on PLGA casts of nanophase carbon fibers. The summation of these results demonstrate that due to a high degree of nanometer surface roughness, carbon fibers with nanometer dimensions may be optimal materials to selectively increase osteoblast adhesion necessary for successful orthopedic/dental implant applications.

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271 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...Osteoblasts cultivated on metallic surfaces with nano- to micro-topography exhibit differences in their adhesion and spreading activity (Deligianni et al., 2001; Lange et al., 2002; Linez-Bataillon et al., 2002; Price et al., 2004)....
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Journal Article•DOI•

Apatite-mediated Actin Dynamics in Resorbing Osteoclasts

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Frédéric Saltel¹, Olivier Destaing¹, Frederic Bard², D. Eichert³, Pierre Jurdic¹ - Show less +1 more•Institutions (3)

Centre national de la recherche scientifique¹, University of California, Los Angeles², European Synchrotron Radiation Facility³

01 Dec 2004-Molecular Biology of the Cell

TL;DR: This work suggests that apatite-mediated sealing zone formation is dependent on both c-src and Rho whereas apico-basal polarization requires only Rho.

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Abstract: The actin cytoskeleton is essential for osteoclasts main function, bone resorption. Two different organizations of actin have been described in osteoclasts, the podosomes belt corresponding to numerous F-actin columns arranged at the cell periphery, and the sealing zone defined as a unique large band of actin. To compare the role of these two different actin organizations, we imaged osteoclasts on various substrata: glass, dentin, and apatite. Using primary osteoclasts expressing GFP-actin, we found that podosome belts and sealing zones, both very dynamic actin structures, were present in mature osteoclasts; podosome belts were observed only in spread osteoclasts adhering onto glass, whereas sealing zone were seen in apico-basal polarized osteoclasts adherent on mineralized matrix. Dynamic observations of several resorption cycles of osteoclasts seeded on apatite revealed that 1) podosomes do not fuse together to form the sealing zone; 2) osteoclasts alternate successive stationary polarized resorption phases with a sealing zone and migration, nonresorption phases without any specific actin structure; and 3) apatite itself promotes sealing zone formation though c-src and Rho signaling. Finally, our work suggests that apatite-mediated sealing zone formation is dependent on both c-src and Rho whereas apico-basal polarization requires only Rho.

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269 citations

"Nano-topography sensing by osteocla..." refers background in this paper

...…cell proliferation, gene expression and cell viability (Bershadsky et al., 2006a; Chen et al., 1997; Diener et al., 2005; Discher et al., 2005; Engler et al., 2006; Geiger et al., 2009; Kunzler et al., 2007; Lo et al., 2000; Roach et al., 2007; Saltel et al., 2004; Vogel and Sheetz, 2006)....
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