Finite-element model of interaction between fungal polysaccharide and monoclonal antibody in the capsule of Cryptococcus neoformans

Vineet Rakesh, Andrew D. Schweitzer, Oscar Zaragoza, Ruth Bryan, Kevin Wong, Ashim Datta, Arturo Casadevall, Ekaterina Dadachova

Research output: Contribution to journalArticle

Abstract

Many microorganisms such as bacteria and fungi possess so-called capsules made of polysaccharides which protect these microorganisms from environmental insults and host immune defenses. The polysaccharide capsule of Cryptococcus neoformans, a human pathogenic yeast, is capable of self-assembly, composed mostly of glucuronoxylomannan (GXM), a polysaccharide with a molecular weight of approximately 2 000 000, and has several layers with different densities. The objective of this study was to model pore-hindered diffusion and binding of the GXM-specific antibody within the C. neoformans capsule. Using the finite-element method (FEM), we created a model which represents the in vivo binding of a GXM-specific antibody to a C. neoformans cell taking into account the intravenous infusion time of antibody, antibody diffusion through capsular pores, and Michaelis-Menten kinetics of antibody binding to capsular GXM. The model predicted rapid diffusion of antibody to all regions of the capsule where the pore size was greater than the Stokes diameter of the antibody. Binding occurred primarily at intermediate regions of the capsule. The GXM concentration in each capsular region was the principal determinant of the steady-state antibody-GXM complex concentration, while the forward binding rate constant influenced the rate of complex formation in each region. The concentration profiles predicted by the model closely matched experimental immunofluorescence data. Inclusion of different antibody isotypes (IgG, IgA, and IgM) into the modeling algorithm resulted in similar complex formation in the outer capsular regions, but different depths of binding at the inner regions. These results have implications for the development of new antibody-based therapies.

Original languageEnglish (US)
Pages (from-to)8514-8522
Number of pages9
JournalJournal of Physical Chemistry B
Volume112
Issue number29
DOIs
StatePublished - Jul 24 2008
Externally publishedYes

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Fingerprint Dive into the research topics of 'Finite-element model of interaction between fungal polysaccharide and monoclonal antibody in the capsule of Cryptococcus neoformans'. Together they form a unique fingerprint.

  • Cite this