Integration column: artificial ECM: expanding the cell biology toolbox in 3D.

Many crucial cellular processes in our tissues are governed by complex, spatio-temporally regulated interactions between cells and their extracellular matrix (ECM). These interactions can be studied using well-established 3D in vitro model systems such as collagen gels or Matrigel generated from native ECM macromolecular components. Recent advances in the molecular design of 'smart' synthetic biomaterials have generated artificial ECM (aECM) that mimic some of the key structural and biochemical characteristics of their naturally derived counterparts and, thanks to their synthetic origin, promise to overcome some complexities of the latter. Here I will discuss emerging approaches in aECM design, hopefully inspiring cell biologists to apply these systems to address their specific biological question.

[1]  P. Friedl,et al.  The biology of cell locomotion within three-dimensional extracellular matrix , 2000, Cellular and Molecular Life Sciences CMLS.

[2]  R. Hynes,et al.  Physiological levels of tumstatin, a fragment of collagen IV alpha3 chain, are generated by MMP-9 proteolysis and suppress angiogenesis via alphaV beta3 integrin. , 2003, Cancer cell.

[3]  M. Bissell,et al.  Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. , 2006, Annual review of cell and developmental biology.

[4]  Matthias P Lutolf,et al.  Biomolecular hydrogels formed and degraded via site-specific enzymatic reactions. , 2007, Biomacromolecules.

[5]  P. Janmey,et al.  Tissue Cells Feel and Respond to the Stiffness of Their Substrate , 2005, Science.

[6]  Derek N Woolfson,et al.  Engineering the morphology of a self-assembling protein fibre , 2003, Nature materials.

[7]  L. Griffith,et al.  Capturing complex 3D tissue physiology in vitro , 2006, Nature Reviews Molecular Cell Biology.

[8]  Kenneth M. Yamada,et al.  Modeling Tissue Morphogenesis and Cancer in 3D , 2007, Cell.

[9]  Jeffrey A. Hubbell,et al.  Polymeric biomaterials with degradation sites for proteases involved in cell migration , 1999 .

[10]  H. Bianco-Peled,et al.  Defining the role of matrix compliance and proteolysis in three-dimensional cell spreading and remodeling. , 2008, Biophysical journal.

[11]  Kevin M. Shakesheff,et al.  Responsive Polymers at the Biology/Materials Science Interface , 2006 .

[12]  G. Whitesides,et al.  Microfabrication meets microbiology , 2007, Nature Reviews Microbiology.

[13]  Krista L. Niece,et al.  Selective Differentiation of Neural Progenitor Cells by High-Epitope Density Nanofibers , 2004, Science.

[14]  Mina J Bissell,et al.  Modeling tissue-specific signaling and organ function in three dimensions , 2003, Journal of Cell Science.

[15]  L G Griffith,et al.  Cell adhesion and motility depend on nanoscale RGD clustering. , 2000, Journal of cell science.

[16]  J. West,et al.  Cell migration through defined, synthetic extracellular matrix analogues , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  K. Anseth,et al.  Hydrogel Cell Cultures , 2007, Science.

[18]  Shuguang Zhang Fabrication of novel biomaterials through molecular self-assembly , 2003, Nature Biotechnology.

[19]  Ali Khademhosseini,et al.  Fabrication of gradient hydrogels using a microfluidics/photopolymerization process. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[20]  Krista L. Niece,et al.  Self-assembly combining two bioactive peptide-amphiphile molecules into nanofibers by electrostatic attraction. , 2003, Journal of the American Chemical Society.

[21]  J. Kopeček,et al.  Hydrogels as smart biomaterials , 2007 .

[22]  Wim E. Hennink,et al.  Novel crosslinking methods to design hydrogels , 2002 .

[23]  P. Friedl Prespecification and plasticity: shifting mechanisms of cell migration. , 2004, Current opinion in cell biology.

[24]  A. Khademhosseini,et al.  Microscale technologies for tissue engineering and biology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[25]  J. Hubbell,et al.  Mechanisms of 3-D migration and matrix remodeling of fibroblasts within artificial ECMs. , 2007, Acta biomaterialia.

[26]  Anna Bershteyn,et al.  Bioactive Hydrogels with an Ordered Cellular Structure Combine Interconnected Macroporosity and Robust Mechanical Properties , 2005 .

[27]  A. Hamilton,et al.  Water gelation by small organic molecules. , 2004, Chemical reviews.

[28]  J. Hubbell,et al.  Recombinant protein-co-PEG networks as cell-adhesive and proteolytically degradable hydrogel matrixes. Part I: Development and physicochemical characteristics. , 2005, Biomacromolecules.

[29]  J. Hartgerink,et al.  Enzyme‐Mediated Degradation of Peptide‐Amphiphile Nanofiber Networks , 2005 .

[30]  Glenn D Prestwich,et al.  Simplifying the extracellular matrix for 3‐D cell culture and tissue engineering: A pragmatic approach , 2007, Journal of cellular biochemistry.

[31]  Jennifer L West,et al.  Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration. , 2005, Biomaterials.

[32]  A. Abbott Cell culture: Biology's new dimension , 2003, Nature.

[33]  J L West,et al.  Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. , 2001, Biomaterials.

[34]  Frederick Grinnell,et al.  Fibroblast biology in three-dimensional collagen matrices. , 2003, Trends in cell biology.

[35]  J. Hubbell,et al.  Molecularly engineered PEG hydrogels: a novel model system for proteolytically mediated cell migration. , 2005, Biophysical journal.

[36]  J. A. Hubbell,et al.  Cell‐Responsive Synthetic Hydrogels , 2003 .

[37]  Shelly R Peyton,et al.  The effects of matrix stiffness and RhoA on the phenotypic plasticity of smooth muscle cells in a 3-D biosynthetic hydrogel system. , 2008, Biomaterials.

[38]  Sangeeta N Bhatia,et al.  Engineering tissues for in vitro applications. , 2006, Current opinion in biotechnology.

[39]  Alyssa Panitch,et al.  Biologically engineered protein-graft-poly(ethylene glycol) hydrogels: a cell adhesive and plasmin-degradable biosynthetic material for tissue repair. , 2002, Biomacromolecules.

[40]  A. Metters,et al.  Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cell-invasion characteristics , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[41]  G. McConnell,et al.  Enzyme responsive polymer hydrogel beads. , 2005, Chemical communications.

[42]  Ralph Müller,et al.  Synthetic extracellular matrices for in situ tissue engineering , 2004, Biotechnology and bioengineering.

[43]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[44]  Denis Wirtz,et al.  Fibronectin fibrillogenesis regulates three-dimensional neovessel formation. , 2008, Genes & development.

[45]  M. Stack,et al.  Selective Hydrolysis of Triple-helical Substrates by Matrix Metalloproteinase-2 and -9* , 2003, The Journal of Biological Chemistry.

[46]  K. Healy,et al.  Synthetic MMP-13 degradable ECMs based on poly(N-isopropylacrylamide-co-acrylic acid) semi-interpenetrating polymer networks. I. Degradation and cell migration. , 2005, Journal of biomedical materials research. Part A.