Intrafibrillar, bone-mimetic collagen mineralization regulates breast cancer cell adhesion and migration

Biomaterials. 2019 Apr;198:95-106. doi: 10.1016/j.biomaterials.2018.05.002. Epub 2018 May 7.


Bone metastasis is a leading cause of death in patients with breast cancer, but the underlying mechanisms are poorly understood. While much work focuses on the molecular and cellular events that drive breast cancer bone metastasis, it is mostly unclear what role bone extracellular matrix (ECM) properties play in this process. Bone ECM primarily consists of mineralized collagen fibrils, which are composed of non-stoichiometric carbonated apatite (HA) and collagen type I. Reduced bone mineral content is epidemiologically linked with increased risk of bone metastasis. Yet elucidating the potential functional impact of collagen mineralization on breast cancer cells has remained challenging because of a lack of model systems that allow studying tumor cell behavior as a function of physiological, intrafibrillar collagen mineralization. Here, we have developed cell culture substrates composed of mineralized collagen type I fibrils using a polymer-induced liquid-precursor (PILP) process. Intrafibrillar HA decreased breast cancer cell adhesion forces and accordingly reduced collagen fiber alignment relative to cells cultured on control collagen. The resulting mineral-mediated changes in collagen network characteristics and mechanosignaling correlated with increased cell motility, but inhibited directed migration of breast cancer cells. These results suggest that physiological mineralization of collagen fibrils reduces tumor cell adhesion with potential functional consequences on skeletal homing of disseminated tumor cells in early stages of breast cancer metastasis.

Keywords: Bone metastasis; Collagen fiber alignment; Hydroxyapatite; Intrafibrillar collagen mineralization; Mechanosignaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apatites / chemistry
  • Biocompatible Materials / chemistry
  • Biomechanical Phenomena
  • Bone Neoplasms / chemistry
  • Bone Neoplasms / secondary
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / pathology*
  • Calcification, Physiologic
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement
  • Collagen Type I / chemistry*
  • Elastic Modulus
  • Female
  • Humans
  • Rats


  • Apatites
  • Biocompatible Materials
  • Collagen Type I