title: Protein-crystal interface mediates cell adhesion and proangiogenic secretion.
abstract: The nanoscale materials properties of bone apatite crystals have been implicated in breast cancer bone metastasis and their interactions with extracellular matrix proteins are likely involved. In this study, we used geologic hydroxyapatite (HAP, Ca10(PO4)6(OH)2), closely related to bone apatite, to investigate how HAP surface chemistry and nano/microscale topography individually influence the crystal-protein interface, and how the altered protein deposition impacts subsequent breast cancer cell activities. We first utilized Förster resonance energy transfer (FRET) to assess the molecular conformation of fibronectin (Fn), a major extracellular matrix protein upregulated in cancer, when it adsorbed onto HAP facets. Our analysis reveals that both low surface charge density and nanoscale roughness of HAP facets individually contributed to molecular unfolding of Fn. We next quantified cell adhesion and secretion on Fn-coated HAP facets using MDA-MB-231 breast cancer cells. Our data show elevated proangiogenic and proinflammatory secretions associated with more unfolded Fn adsorbed onto nano-rough HAP facets with low surface charge density. These findings not only deconvolute the roles of crystal surface chemistry and topography in interfacial protein deposition but also enhance our knowledge of protein-mediated breast cancer cell interactions with apatite, which may be implicated in tumor growth and bone metastasis.
authors.affiliation: Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, USA. Electronic address: fw225@cornell.edu.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Weisi
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Gillis
authors.affiliation: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA; Kavli Institute at Cornell for Nanoscale Science, Ithaca, NY 14853, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fischbach
authors.affiliation: Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, USA; Kavli Institute at Cornell for Nanoscale Science, Ithaca, NY 14853, USA.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Estroff
authors.affiliation: Department of Materials Science and Engineering, Cornell University, Ithaca, NY 14853, USA; Department of Physics, University of Ottawa, Ottawa, ON K1N 6N5, Canada. Electronic address: dg434@cornell.edu.
authors.forename: Delphine
authors.initials: D
authors.lastname: Gourdon
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003460:Crystallization / Q000379:methods; D017886:Durapatite / Q000737:chemistry*; D005353:Fibronectins / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D013499:Surface Properties
chemical_list: D042501:Angiogenic Proteins; D005353:Fibronectins; D017886:Durapatite
keywords: Breast cancer cells; Fibronectin; Hydroxyapatite; Nano/microscale topography; Protein-crystal interactions; Surface chemistry