UFOs, Worms, and Surfboards: What Shapes Teach Us About Cell–Material Interactions

  • Julie A. Champion
  • Samir MitragotriEmail author
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)


The success of regenerative materials is dependent on the ability to elicit cell interactions. Cell–material interactions, both desired and undesired, are dictated by the physical properties of the material. Previous research has focused on surface chemistry and feature size of biomaterials. The role of shape, in particular the ability of cells to recognize and respond to shape, has not been determined. This is primarily due to the limited availability of techniques to produce materials with features of controlled and varied morphologies. To this end, we have created a diverse collection of novel polymer micro- and nano-particle shapes and studied their phagocytosis by macrophages. The macrophage immune response to biomaterials is a formidable obstacle in delivery and integration of materials for successful tissue regeneration, engineering, and drug delivery. The results show that particle shape, from the point of view of the macrophage, profoundly impacts phagocytosis, more than particle size and independent of surface chemistry. We can use this understanding to design material features that will direct desired macrophage response and, in the future, study the effects of shape on other cell functions. This work demonstrates the importance of shape in the design of biomaterials and its influence on cell–material interactions.


Shape Microspheres Drug delivery Phagocytosis 


  1. Aderem A, Underhill DM (1999) Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 17(1):593–623CrossRefGoogle Scholar
  2. Aizawa H, Fukui Y, Yahara I (1997) Live dynamics of Dictyostelium cofilin suggests a role in remodeling actin latticework into bundles. J Cell Sci 110(19):2333–2344Google Scholar
  3. Arredouani MS, Palecanda A, Koziel H, Huang YC, Imrich A, Sulahian TH, Ning YY, Yang ZP, Pikkarainen T, Sankala M, Vargas SO, Takeya M, Tryggvason K, Kobzik L (2005) MARCO is the major binding receptor for unopsonized particles and bacteria on human alveolar macrophages. J Immunol 175(9):6058–6064Google Scholar
  4. Ball MD, Prendergast U, O’Connell C, Sherlock R (2007) Comparison of cell interactions with laser machined micron- and nanoscale features in polymer. Exp Mol Pathol 82(2):130–134CrossRefGoogle Scholar
  5. Cannon GJ, Swanson JA (1992) The macrophage capacity for phagocytosis. J Cell Sci 101(4):907–913Google Scholar
  6. Castellano F, Chavrier P, Caron E (2001) Actin dynamics during phagocytosis. Semin Immunol 13(6):347–355CrossRefGoogle Scholar
  7. Champion JA, Katare YK, Mitragotri S (2007a) Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers. J Control Release 121(1–2):3–9CrossRefGoogle Scholar
  8. Champion JA, Katare YK, Mitragotri S (2007b) Making polymeric micro- and nanoparticles of complex shapes. Proc Natl Acad Sci USA 104(29):11901–11904CrossRefGoogle Scholar
  9. Cougoule C, Wiedemann A, Lim J, Caron E (2004) Phagocytosis, an alternative model system for the study of cell adhesion. Semin Cell Dev Biol 15(6):679–689Google Scholar
  10. Dunne M, Corrigan OI, Ramtoola Z (2000) Influence of particle size and dissolution conditions on the degradation properties of polylactide-co-glycolide particles. Biomaterials 21(16):1659–1668CrossRefGoogle Scholar
  11. Geng Y, Dalhaimer P, Cai S, Tsai R, Tewari M, Minko T, Discher DE (2007) Shape effects of filaments versus spherical particles in flow and drug delivery. Nat Nanotechnol 2(4):249–255CrossRefGoogle Scholar
  12. Goldsby RA, Kindt TJ, Osborne BA, Kuby J (2003) Immunology. Freeman, New YorkGoogle Scholar
  13. Goldsmith HL, Turitto VT (1986) Rheological aspects of thrombosis and hemostasis - basic principles and applications. Thromb Haemost 55(3):415–435Google Scholar
  14. Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R (1994) Biodegradable long-circulating polymeric nanospheres. Science 263(5153):1600–1603CrossRefGoogle Scholar
  15. Hetland G, Namork E, Schwarze PE, Aase A (2000) Mechanism for uptake of silica particles by monocytic U937 cells. Hum Exp Toxicol 19(7):412–419CrossRefGoogle Scholar
  16. Ho CC, Keller A, Odell JA, Ottewill RH (1993) Preparation of monodisperse ellipsoidal polystyrene particles. Colloid Polym Sci 271(5):469–479CrossRefGoogle Scholar
  17. Illum L, Davis SS, Wilson CG, Thomas NW, Frier M, Hardy JG (1982) Blood clearance and organ deposition of intravenously administered colloidal particles – the effects of particle size, nature and shape. Int J Pharm 12(2–3):135–146CrossRefGoogle Scholar
  18. Israelchvili J (1992) Intermolecular and surface forces. Academic, San Diego, CAGoogle Scholar
  19. Kawaguchi H, Koiwai N, Ohtsuka Y, Miyamoto M, Sasakawa S (1986) Phagocytosis of latex-particles by leukocytes. 1. Dependence of phagocytosis on the size and surface-potential of particles. Biomaterials 7(1):61–66CrossRefGoogle Scholar
  20. Koval M, Preiter K, Adles C, Stahl PD, Steinberg TH (1998) Size of IgG-opsonized particles determines macrophage response during internalization. Exp Cell Res 242(1):265–273CrossRefGoogle Scholar
  21. Lamprecht A, Schafer U, Lehr CM (2001) Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa. Pharm Res 18(6):788–793CrossRefGoogle Scholar
  22. Langer R (1990) New methods of drug delivery. Science 249(4976):1527–1533CrossRefGoogle Scholar
  23. Lee E, Shelden EA, Knecht DA (1997) Changes in actin filament organization during pseudopod formation. Exp Cell Res 235(1):295–299CrossRefGoogle Scholar
  24. Lee EY, Pang KM, Knecht D (2001) The regulation of actin polymerization and cross-linking in Dictyostelium. Biochim Biophys Acta 1525(3):217–227CrossRefGoogle Scholar
  25. Liang HF, Chen CT, Chen SC, Kulkarni AR, Chiu YL, Chen MC, Sung HW (2006) Paclitaxel-loaded poly(gamma-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Biomaterials 27(9):2051–2059CrossRefGoogle Scholar
  26. Manning MC, Patel K, Borchardt RT (1989) Stability of protein pharmaceuticals. Pharm Res 6(11):903–918CrossRefGoogle Scholar
  27. May RC, Machesky LM (2001) Phagocytosis and the actin cytoskeleton. J Cell Sci 114(6):1061–1077Google Scholar
  28. Moghimi SM, Hunter AC, Murray JC (2001) Long-circulating and target-specific nanoparticles: theory to practice. Pharm Rev 53(2):283–318Google Scholar
  29. Mohraz A, Solomon MJ (2005) Direct visualization of colloidal rod assembly by confocal microscopy. Langmuir 21(12):5298–5306CrossRefGoogle Scholar
  30. O’Brien DK, Melville SB (2003) Multiple effects on Clostridium perfringens binding, uptake and trafficking to lysosomes by inhibitors of macrophage phagocytosis receptors. Microbiol SGM 149:1377–1386CrossRefGoogle Scholar
  31. Painter PC, Coleman MM (1997) Fundamentals of polymer science. CRC, Boca Raton, FLGoogle Scholar
  32. Panyam J, Dali MA, Sahoo SK, Ma WX, Chakravarthi SS, Amidon GL, Levy RJ, Labhasetwar V (2003) Polymer degradation and in vitro release of a model protein from poly(d, l-lactide-co-glycolide) nano- and microparticles. J Control Release 92(1–2):173–187CrossRefGoogle Scholar
  33. Patil VRS, Campbell CJ, Yun YH, Slack SM, Goetz DJ (2001) Particle diameter influences adhesion under flow. Biophys J 80(4):1733–1743CrossRefGoogle Scholar
  34. Patri AK, Majoros IJ, Baker JR (2002) Dendritic polymer macromolecular carriers for drug delivery. Curr Opin Chem Biol 6(4):466–471CrossRefGoogle Scholar
  35. Pearson AM (1996) Scavenger receptors in innate immunity. Curr Opin Immunol 8(1):20–28CrossRefGoogle Scholar
  36. Poste G, Kirsh R (1983) Site-specific (targeted) drug delivery in cancer-therapy. Biotechnology 1(10):869–878CrossRefGoogle Scholar
  37. Prausnitz MR, Mitragotri S, Langer R (2004) Current status and future potential of transdermal drug delivery. Nat Rev Drug Discov 3(2):115–124CrossRefGoogle Scholar
  38. Reddy GR, Bhojani MS, McConville P, Moody J, Moffat BA, Hall DE, Kim G, Koo YEL, Woolliscroft MJ, Sugai JV, Johnson TD, Philbert MA, Kopelman R, Rehemtulla A, Ross BD (2006) Vascular targeted nanoparticles for imaging and treatment of brain tumors. Clin Cancer Res 12(22):6677–6686CrossRefGoogle Scholar
  39. Rejman J, Oberle V, Zuhorn IS, Hoekstra D (2004) Size-dependent internalization of particles via the pathways of clathrin-and caveolae-mediated endocytosis. Biochem J 377:159–169CrossRefGoogle Scholar
  40. Roff WJ, Scott JR (1971) Fibres, films, plastics and rubbers. Butterworths, LondonGoogle Scholar
  41. Rolland JP, Maynor BW, Euliss LE, Exner AE, Denison GM, DeSimone JM (2005) Direct fabrication and harvesting of monodisperse, shape-specific nanobiomaterials. J Am Chem Soc 127(28):10096–10100CrossRefGoogle Scholar
  42. Ross JA, Auger MJ (2002) The biology of the macrophage. In: Burke B, Lewis CE (eds) The macrophage. Oxford University Press, OxfordGoogle Scholar
  43. Rudt S, Muller RH (1993) In vitro phagocytosis assay of nano- and microparticles by chemiluminescence. 3. Uptake of differently sized surface-modified particles, and its correlation to particle properties and in vivo distribution. Eur J Pharm Sci 1(1):31–39CrossRefGoogle Scholar
  44. Simon SI, Schmidschonbein GW (1988) Biophysical aspects of microsphere engulfment by human-neutrophils. Biophys J 53(2):163–173CrossRefGoogle Scholar
  45. Stolnik S, Illum L, Davis SS (1995) Long circulating microparticulate drug carriers. Adv Drug Deliv Rev 16(2–3):195–214CrossRefGoogle Scholar
  46. Storm G, Belliot SO, Daemen T, Lasic DD (1995) Surface modification of nanoparticles to oppose uptake by the mononuclear phagocyte system. Adv Drug Deliv Rev 17(1):31–48CrossRefGoogle Scholar
  47. Swanson JA, Hoppe AD (2004) The coordination of signaling during Fc receptor-mediated phagocytosis. J Leukoc Biol 76(6):1093–1103CrossRefGoogle Scholar
  48. Tabata Y, Ikada Y (1990) Phagocytosis of polymer microspheres by macrophages. Adv Polym Sci 94:107–141CrossRefGoogle Scholar
  49. Welch MD, Mullins RD (2002) Cellular control of actin nucleation. Annu Rev Cell Dev Biol 18:247–288CrossRefGoogle Scholar
  50. Yim EK, Leong KW (2005) Significance of synthetic nanostructures in dictating cellular response. Nanomedicine 1(1):10–21CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.School of Chemical and Biomolecular EngineeringGeorgia Institute of TechnologyAtlantaUSA
  2. 2.Department of Chemical EngineeringUniversity of California Santa BarbaraSanta BarbaraUSA

Personalised recommendations