Surface-catalyzed amyloid fibril formation

J Biol Chem. 2002 Dec 27;277(52):50914-22. doi: 10.1074/jbc.M207225200. Epub 2002 Sep 27.

Abstract

Light chain (or AL) amyloidosis is characterized by the pathological deposition of insoluble fibrils of immunoglobulin light chain fragments in various tissues, walls of blood vessels, and basement membranes. In the present investigation, the in vitro assembly of a recombinant amyloidogenic light chain variable domain, SMA, on various surfaces was monitored using atomic force microscopy. SMA formed fibrils on native mica at pH 5.0, conditions under which predominantly amorphous aggregates form in solution. Fibril formation was accelerated significantly on surfaces compared with solution; for example, fibrils grew on surfaces at significantly faster rates and at much lower concentrations than in solution. No fibrils were observed on hydrophobic or positively charged surfaces or at pH >7.0. Two novel types of fibril growth were observed on the surface: bidirectional linear assembly of oligomeric units, and linear growth from preformed amorphous cores. In addition to catalyzing the rate of fibrillation, the mechanism of fibril formation on the surfaces was significantly different from in solution, but it may be more physiologically relevant because in vivo the deposits are associated with surfaces.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / ultrastructure
  • Amyloidosis / pathology
  • Basement Membrane / pathology
  • Humans
  • Immunoglobulin Light Chains / blood
  • Kinetics
  • Microfibrils / chemistry
  • Microfibrils / ultrastructure
  • Microscopy, Atomic Force
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Immunoglobulin Light Chains
  • Recombinant Proteins