1 / 29

Outline

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.

tuyen
Download Presentation

Outline

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related