Label-Free and Direct Visualization of Multivalent Binding of Bone Morphogenetic Protein-2 with Cartilage Oligomeric Matrix Protein

Victoria Tran, Arpad Karsai, Michael C. Fong, Weiliang Cai, Jasper H.N. Yik, Eric Otto Klineberg, Dominik R Haudenschild, Gang-yu Liu

Research output: Contribution to journalArticle

Abstract

This work presents the first direct evidence of multivalent binding between bone morphogenetic protein-2 (BMP-2) and cartilage oligomeric matrix protein (COMP) using high-resolution atomic force microscopy (AFM) imaging. AFM topographic images reveal the molecular morphology of COMP, a pentameric protein whose five identical monomer units bundle together at N-termini, extending out with flexible chains to C-termini. Upon addition of BMP-2, COMP molecules undergo conformational changes at the C-termini to enable binding with BMP-2 molecules. AFM enables local structural changes of COMP to be revealed upon binding various numbers, 1-5, of BMP-2 molecules. These BMP-2/COMP complexes exhibit very different morphologies from those of COMP: much more compact and thus less flexible. These molecular-level insights deepen current understanding of the mechanism of how the BMP-2/COMP complex enhances osteogenesis among osteoprogenitor cells, i.e., multivalent presentation of BMP-2 via the stable and relatively rigid BMP-2/COMP complex could form a lattice of interaction between multiple BMP-2 and BMP-2 receptors. These ligand-receptor clusters lead to fast initiation and sustained activation of the Smad signaling pathway, resulting in enhanced osteogenesis. This work is also of translational importance as the outcome may enable use of lower BMP-2 dosage for bone repair and regeneration.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalJournal of Physical Chemistry B
Volume123
Issue number1
DOIs
StatePublished - Oct 1 2019

Fingerprint

Cartilage Oligomeric Matrix Protein
Bone Morphogenetic Protein 2
cartilage
Cartilage
bones
Labels
Bone
Visualization
proteins
Proteins
matrices
Atomic Force Microscopy
Atomic force microscopy
Osteogenesis
Molecules
osteogenesis
Bone Morphogenetic Protein Receptors
Bone Regeneration
atomic force microscopy

ASJC Scopus subject areas

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

Cite this

Label-Free and Direct Visualization of Multivalent Binding of Bone Morphogenetic Protein-2 with Cartilage Oligomeric Matrix Protein. / Tran, Victoria; Karsai, Arpad; Fong, Michael C.; Cai, Weiliang; Yik, Jasper H.N.; Klineberg, Eric Otto; Haudenschild, Dominik R; Liu, Gang-yu.

In: Journal of Physical Chemistry B, Vol. 123, No. 1, 01.10.2019, p. 39-46.

Research output: Contribution to journalArticle

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