Cell-Matrix Adhesion


The extracellular matrix and the basal lamina[Edit]

Cell-matrix adhesion is the interaction of a cell with the extracellular matrix, mediated by multi-protein adhesion structures such as focal adhesions, fibrillar adhesions and podosomes. 

The ECM is a network of extracellular molecules which are secreted locally to ensure cell and tissue cohesion. The ECM also serves as a reservoir for extracellular signaling molecules that control cell growth, migration, and differentiation. The major classes of ECM molecules are proteoglycans, collagens and multi-adhesive matrix proteins (e.g. laminin, fibronectin). In mammals, the ECM is commonly known as "connective tissue". ECM components are linked to each other through diverse protein and carbohydrate-binding domains. For stability in tissues, cells are linked to the ECM through cell adhesion receptors (e.g. integrins). A specialized form of extracellular matrix that underlies the basal side of polarized epithelial cell sheets to separate them from the underlying connective tissue is the basal lamina [1]. 

Basal laminae (plural) also surround individual muscle cells, fat cells, and cells lining peripheral nerve cell axons (i.e. Schwann cells) [1]. The basal lamina is thin and flexible, and is composed of closely packed matrix molecules that lack significant volume. The basal lamina components are synthesized and deposited by the cells on either side: the epithelial cells and the cells within the underlying bed of connective tissue (i.e. fibroblasts). The basal laminae forms a cohesive network and mechanical connection between cells and their external environment. Force-driven signals originating between the basal lamina components (i.e. fibronectin) and linked cell adhesion receptors (i.e. integrins) is communicated to the interior of cells through a mechanotransduction system to influence cell polarity, metabolism, fate, and migration.

The key constituents found in the basal lamina are glycoproteins (i.e. laminin, collagen) and proteoglycans (i.e. perlecan), however, the precise composition varies from tissue to tissue and various other molecules (e.g. fibronectin) can also be found [1].

What are cell-matrix adhesions?[Edit]

Cell-matrix interactions are mediated by adhesion receptors and lead to the formation of multi-protein adhesion structures that interact with the actin cytoskeleton at the cell interior; collectively, they are called cell-matrix adhesion complexes (CMACs) [2]. 
Figure 1. Types of cell-matrix adhesion complexes
These adhesions act as vital information processing centers that enable cells to sense numerous extracellular signals that convey information about the chemistry, geometry, and physical properties of the ECM (reviewed in [3]). The substrate type or chemical composition (reviewed in [4]), its rigidity [5, 6], and the surface topography [7, 8, 9](reviewed in [10, 11, 12]) influence force-induced events through CMACs, and mechanosensitive cells transmit this information through subsequent mechanotransduction pathways and signaling cascades to influence diverse processes such as the cell shape, polarity, fate, motility and deposition and/or restructuring of ECM components [5, 13, 14, 15] (reviewed in [3, 11, 16, 17]).

What are focal adhesions?[Edit]

Focal adhesions are the best-characterized among the different types of CMACs and are known to occur in different adhesion stages depending on the position and interplay of internal and external forces. FAs are known to evolve into fibrillar adhesions (FBs), which promote reorganization of the ECM while moving towards the center of the cell (reviewed in [18]). They are also capable of transforming into podosomes under certain conditions [19]. Such transitions could be of remarkable significance under physiological conditions.

CMACs are highly dynamic and flexible, with their protein content ranging from a few components to over 100 different proteins (reviewed in [3, 20, 21]). They are assembled, disassembled, and translocated during cell spreading, polarization, migration, and division. The various types of CMACs not only differ in their basic features such as size, location, and shape, but they also differ in their composition, dynamics, component turnover and linkage to F-actin [22, 23]. It should be noted that:

    * not all adhesions may be present within the same cell at the same time
    * the relative level of adhesion types may vary (e.g. during cell motility, differentiation)
    * the presence (or relative level) of a particular adhesion may be cell type- or tissue-specific

Function

Cell binding to ECM components also mediates the assembly of cell-matrix adhesions during cell migration. For example; filopodia attach to ECM components through integrin receptors, allowing these structures to probe the stiffness of the environment around them and promote migration [24]. Integrin molecules accumulate within filopodia to mediate the initial cell-matrix adhesions [25]. In addition, basal adhesions to laminin anchor the filopodial base, which usually remains immobile despite considerable flexibility in the shaft [26].

Tension that is generated between the cytoskeletal network (via the action of contractile stress fibers), linked ECM and focal adhesions controls the cells ability to migrate and protrude filopodia. Cell-matrix adhesion therefore functions as a molecular ‘clutch’ to convert intracellular cytoskeletal assembly into protrusion and movement [27]. Cells also interact with and modify ECM components mechanically, as well as chemically, to alter their alignment and composition in ways that influence cell fate, movement, polarization, and shape. E.g. through the secretion of matricellular proteins that alter ECM composition, which in turns affects cell morphology [28].

What are fibrillar adhesions[Edit]

Fibrillar adhesions are cell-matrix adhesion structures, that are located towards the center of a cell and are believed to evolve from mature focal adhesions. They are bound specifically to fibronectin via α5β1-integrins [29] and appear as long streaks or an array of dots [23, 18]. Fibrillar adhesions are mainly composed of thin actin cables that are crosslinked by the actin binding protein, tensin, and lack linkage to stress fibers [30, 22].

Steps in Formation

Fibrillar adhesions arise from the medial ends of growing focal adhesions at sites where α5β1-integrins translocated out of these complexes centripetally along the underlying fibronectin fibres [31]. The amount of tensin that is bound to the fibrillar adhesions increases as they are translocated [29, 32]. This directional movement towards the cell center causes stretching of the bound fibronectin dimers fibrils in the extracellular matrix (ECM) and promotes its reorganization into fibrils, driven by Rho GTPase activation of actomyosin contractility [32, 33](reviewed in [34]).

The physical state of the extracellular matrix also influences the formation of fibrillar adhesions [30] in the same way as on focal adhesions. The translocation of pliant matrix components (such as fibronectin) and increased cellular tension from the actin cables to the translocating integrins and associated fibronectin molecules is suggested to initiate fibronectin fibrillogenesis and FB assembly [29].

Fibrillar adhesions are distinguished from FAs by the high levels of tensin and low levels or absence of phosphotyrosine [30, 22, 35]. They also lack attachment to stress fibres and do not diassemble when the force is relaxed [32]. Integrin linked kinase (ILK) and the complex it forms with cytoskeleton adaptor proteins, PINCH1 and parvin, are thought to be essential for the transition from early focal adhesions to fibrillar adhesions [36]. This IPP complex functions to reinforce α5β1-actin linkage and provide a platform for tensin and zyxin recruitment.

Controversial evidences exist for the role of FAK-Src signaling pathway in regulating fibrillar adhesions and fibrillogenesis. Some studies report that loss of Src family kinases or FAK activity increases tensin recruitment [37], while in others, similar mutants show reduced efficiency in assembling fibronectin into fibrils [38, 39].

References

  1. Erickson AC., Couchman JR. Still more complexity in mammalian basement membranes. J. Histochem. Cytochem. 2000; 48(10). [PMID: 10990484]
  2. Lock JG., Wehrle-Haller B., Strömblad S. Cell-matrix adhesion complexes: master control machinery of cell migration. Semin. Cancer Biol. 2008; 18(1). [PMID: 18023204]
  3. Geiger B., Spatz JP., Bershadsky AD. Environmental sensing through focal adhesions. Nat. Rev. Mol. Cell Biol. 2009; 10(1). [PMID: 19197329]
  4. Hersel U., Dahmen C., Kessler H. RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials 2003; 24(24). [PMID: 12922151]
  5. Discher DE., Janmey P., Wang YL. Tissue cells feel and respond to the stiffness of their substrate. Science 2005; 310(5751). [PMID: 16293750]
  6. Engler AJ., Sen S., Sweeney HL., Discher DE. Matrix elasticity directs stem cell lineage specification. Cell 2006; 126(4). [PMID: 16923388]
  7. Curtis A., Wilkinson C. New depths in cell behaviour: reactions of cells to nanotopography. Biochem. Soc. Symp. 1999; 65. [PMID: 10320930]
  8. Dalby MJ., Riehle MO., Johnstone H., Affrossman S., Curtis AS. In vitro reaction of endothelial cells to polymer demixed nanotopography. Biomaterials 2002; 23(14). [PMID: 12069336]
  9. Parker KK., Brock AL., Brangwynne C., Mannix RJ., Wang N., Ostuni E., Geisse NA., Adams JC., Whitesides GM., Ingber DE. Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces. FASEB J. 2002; 16(10). [PMID: 12153987]
  10. Vogel V., Sheetz M. Local force and geometry sensing regulate cell functions. Nat. Rev. Mol. Cell Biol. 2006; 7(4). [PMID: 16607289]
  11. Curtis A., Riehle M. Tissue engineering: the biophysical background. Phys Med Biol 2001; 46(4). [PMID: 11324976]
  12. Spatz JP., Geiger B. Molecular engineering of cellular environments: cell adhesion to nano-digital surfaces. Methods Cell Biol. 2007; 83. [PMID: 17613306]
  13. Cavalcanti-Adam EA., Volberg T., Micoulet A., Kessler H., Geiger B., Spatz JP. Cell spreading and focal adhesion dynamics are regulated by spacing of integrin ligands. Biophys. J. 2007; 92(8). [PMID: 17277192]
  14. Gupton SL., Waterman-Storer CM. Spatiotemporal feedback between actomyosin and focal-adhesion systems optimizes rapid cell migration. Cell 2006; 125(7). [PMID: 16814721]
  15. Keren K., Pincus Z., Allen GM., Barnhart EL., Marriott G., Mogilner A., Theriot JA. Mechanism of shape determination in motile cells. Nature 2008; 453(7194). [PMID: 18497816]
  16. Chiquet M., Gelman L., Lutz R., Maier S. From mechanotransduction to extracellular matrix gene expression in fibroblasts. Biochim. Biophys. Acta 2009; 1793(5). [PMID: 19339214]
  17. Schwartz MA., DeSimone DW. Cell adhesion receptors in mechanotransduction. Curr. Opin. Cell Biol. 2008; 20(5). [PMID: 18583124]
  18. Geiger B., Yamada KM. Molecular architecture and function of matrix adhesions. Cold Spring Harb Perspect Biol 2011; 3(5). [PMID: 21441590]
  19. Huveneers S., Arslan S., van de Water B., Sonnenberg A., Danen EH. Integrins uncouple Src-induced morphological and oncogenic transformation. J. Biol. Chem. 2008; 283(19). [PMID: 18326486]
  20. Zaidel-Bar R., Itzkovitz S., Ma'ayan A., Iyengar R., Geiger B. Functional atlas of the integrin adhesome. Nat. Cell Biol. 2007; 9(8). [PMID: 17671451]
  21. Zamir E., Geiger B. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell. Sci. 2001; 114(Pt 20). [PMID: 11707510]
  22. Zaidel-Bar R., Ballestrem C., Kam Z., Geiger B. Early molecular events in the assembly of matrix adhesions at the leading edge of migrating cells. J. Cell. Sci. 2003; 116(Pt 22). [PMID: 14576354]
  23. Zaidel-Bar R., Cohen M., Addadi L., Geiger B. Hierarchical assembly of cell-matrix adhesion complexes. Biochem. Soc. Trans. 2004; 32(Pt3). [PMID: 15157150]
  24. Galbraith CG., Yamada KM., Galbraith JA. Polymerizing actin fibers position integrins primed to probe for adhesion sites. Science 2007; 315(5814). [PMID: 17303755]
  25. Partridge MA., Marcantonio EE. Initiation of attachment and generation of mature focal adhesions by integrin-containing filopodia in cell spreading. Mol. Biol. Cell 2006; 17(10). [PMID: 16855018]
  26. Steketee MB., Tosney KW. Three functionally distinct adhesions in filopodia: shaft adhesions control lamellar extension. J. Neurosci. 2002; 22(18). [PMID: 12223561]
  27. Hoffmann B., Schäfer C. Filopodial focal complexes direct adhesion and force generation towards filopodia outgrowth. Cell Adh Migr undefined; 4(2). [PMID: 20168085]
  28. Regulation of interactions between cells and extracellular matrix: a command performance on several stages. J. Clin. Invest. 2001; 107(7). [PMID: 11285292]
  29. Pankov R., Cukierman E., Katz BZ., Matsumoto K., Lin DC., Lin S., Hahn C., Yamada KM. Integrin dynamics and matrix assembly: tensin-dependent translocation of alpha(5)beta(1) integrins promotes early fibronectin fibrillogenesis. J. Cell Biol. 2000; 148(5). [PMID: 10704455]
  30. Katz BZ., Zamir E., Bershadsky A., Kam Z., Yamada KM., Geiger B. Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Mol. Biol. Cell 2000; 11(3). [PMID: 10712519]
  31. Smilenov LB., Mikhailov A., Pelham RJ., Marcantonio EE., Gundersen GG. Focal adhesion motility revealed in stationary fibroblasts. Science 1999; 286(5442). [PMID: 10550057]
  32. Zamir E., Katz M., Posen Y., Erez N., Yamada KM., Katz BZ., Lin S., Lin DC., Bershadsky A., Kam Z., Geiger B. Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. Nat. Cell Biol. 2000; 2(4). [PMID: 10783236]
  33. Zhong C., Chrzanowska-Wodnicka M., Brown J., Shaub A., Belkin AM., Burridge K. Rho-mediated contractility exposes a cryptic site in fibronectin and induces fibronectin matrix assembly. J. Cell Biol. 1998; 141(2). [PMID: 9548730]
  34. Huveneers S., Danen EH. Adhesion signaling - crosstalk between integrins, Src and Rho. J. Cell. Sci. 2009; 122(Pt 8). [PMID: 19339545]
  35. Zamir E., Katz BZ., Aota S., Yamada KM., Geiger B., Kam Z. Molecular diversity of cell-matrix adhesions. J. Cell. Sci. 1999; 112 ( Pt 11). [PMID: 10318759]
  36. Stanchi F., Grashoff C., Nguemeni Yonga CF., Grall D., Fässler R., Van Obberghen-Schilling E. Molecular dissection of the ILK-PINCH-parvin triad reveals a fundamental role for the ILK kinase domain in the late stages of focal-adhesion maturation. J. Cell. Sci. 2009; 122(Pt 11). [PMID: 19435803]
  37. Volberg T., Romer L., Zamir E., Geiger B. pp60(c-src) and related tyrosine kinases: a role in the assembly and reorganization of matrix adhesions. J. Cell. Sci. 2001; 114(Pt 12). [PMID: 11493667]
  38. Wierzbicka-Patynowski I., Schwarzbauer JE. Regulatory role for SRC and phosphatidylinositol 3-kinase in initiation of fibronectin matrix assembly. J. Biol. Chem. 2002; 277(22). [PMID: 11912200]
  39. Ilić D., Furuta Y., Kanazawa S., Takeda N., Sobue K., Nakatsuji N., Nomura S., Fujimoto J., Okada M., Yamamoto T. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 1995; 377(6549). [PMID: 7566154]
Updated on: Thu, 28 Aug 2014 09:03:02 GMT