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Cell migration at biointerfaces Dr. Prabhas Moghe Biointerfacial Characterization 125:583 September 18, 2006

Cell migration at biointerfaces Dr. Prabhas Moghe Biointerfacial Characterization 125:583 September 18, 2006. Outline. Importance of Cell Migration Modes of cell migration Cell migration and cell adhesion Methods to quantify cell migration Cell migration on dynamic biointerfaces.

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Cell migration at biointerfaces Dr. Prabhas Moghe Biointerfacial Characterization 125:583 September 18, 2006

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  1. Cell migration at biointerfacesDr. Prabhas MogheBiointerfacial Characterization125:583September 18, 2006

  2. Outline • Importance of Cell Migration • Modes of cell migration • Cell migration and cell adhesion • Methods to quantify cell migration • Cell migration on dynamic biointerfaces

  3. Significance of studying cell motility • Cell motility is key to: • Wound healing/repair (quality and kinetics) • Tissue adhesion and turnover on implanted materials • Cancer invasiveness/metastasis • Sorting of cells during development/embryogenesis • White blood and immune cell functions

  4. Modes of Cell Migration - A Primer Simplest Classification: Random Motility versus Chemotaxis S: Cell Speed P: Directional Persistence (a) Random Motility: No orientation bias is exhibited with respect to S or P. (b) Topotaxis: Biased turning toward gradient direction (shown toward right) (c) Orthotaxis: Enhanced S when the cell is oriented in the gradient direction, (d): Klinotaxis: Decreased P when the cell is oriented in the gradient direction (e): Orthokinesis: S decreases with increasing stimulus concentration (f) Klinokinesis: P increases with increasing stimulus concentration

  5. Cell MigrationIndirect Methods • Under-Agarose Assay • Membrane Infiltration Assay (Millipore/Boyden) • 3-D Conjoined Gel Assay •  Orientation Assay (Zigmond)

  6. Under-Agarose Assay Cell Migration Assays Filter Assay Conjoined Gel Assay

  7. Molecular View of Cell Adhesion

  8. Strength of Adhesion & Receptor-Ligand Affinity Kuo SC. Lauffenburger DA. Relationship between receptor/ligand binding affinity and adhesion strength. [Journal Article] Biophysical Journal. 65(5):2191-200, 1993 Nov.

  9. Relation between cell adhesion and cell migrationDiMilla et al., JCB, 1992

  10. Cell migration & cell adhesive strengthPalecek et al., Nature 385:537 (1997)

  11. 3-D Cell migration Biophys J. 2005 Aug;89(2):1389-97. Epub 2005 May 20.

  12. Cell Migration Analysis on Biomaterials: Direct Methods Biophys J. 1992 Feb;61(2):306-15. Biophys J. 1997 Mar;72(3):1472-80.

  13. Direct Migration Methods, Contd.

  14. Theory of Cell Migration:Indirect Assays • Cell Population Migration is described in terms of objective migratory parameters, m, and c. These parameters do not vary with system size, time of incubation, etc. m = random motility coefficient (cm2/s) c = chemotaxis coefficient (cm2/s-M) • Two fundamental equations are required: - Cell transport equation (captures migration behavior) - Cell conservation equation

  15. Theory of Cell Migration • Cell Migration in an Isotropic Environment (Random Migration): where c is the cell density and a is the concentration of soluble stimulant concentration (if any). • Cell conservation equation: • Overall equation:

  16. Solution to Cell Migration Model C(x,t) Co time, t x Solution: If where )=1) (Note, erf(0)=0; erf(

  17. Example of m variation with biomaterial substrate • Human Neutrophils on ePTFE, a vascular prosthetic material, treated with different plasma proteins, and in the presence of the chemoattractant, formyl-methionyl-leucyl- phenylalanine (fMLP). Chang, C., Lieberman, S., and Moghe, P.V., J. Mat. Sci. Mat. Med. 11: 337 (2000)

  18. Protein interface on biomaterials shifts the directional motility of cells Chang, C., Lieberman, S., and Moghe, P.V., J. Mat. Sci. Mat. Med. 11: 337 (2000)

  19. Cell migration on anisotropic substrates • Cell migration under flow • Cell migration on oriented textured substrates • Cell migration on substrates with chemical, electrical, stiffness gradients.

  20. Analysis of Cell Motility on Biosubstrates under Flow Rosenson-Schloss et al, J. Biomed. Mater. Res., 60:8, 2002 ’

  21. Quantitation of Cell Migration under Flow

  22. Cell migration on dynamic biointerfaces (ligand-nanoparticles)Tjia and Moghe, Tissue Eng, 8: 247 (2002); Annals of Biomed. Eng, 30: 851 (2002)

  23. Cell motility behavior characterization as a function of ligand-microparticle density (Tjia and Moghe, Tissue Eng., 2002)

  24. Cell motility behavior characterization, continued

  25. Mathematical description of cell motility and ligand binding (Tjia & Moghe, ABE, 2002)

  26. Kinetics of ligand binding and internalization within motile cells

  27. Cell motility correlates with matrix ligand sampling

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