title: Substrate mineralization stimulates focal adhesion contact redistribution and cell motility of bone marrow stromal cells.
abstract: Understanding the mechanisms of substrate based control of cell function is critical to the design of biomaterials. Cells interact with their extracellular matrix through cell adhesion contacts. We have previously described the self assembly of bone-like mineral onto an organic template and have shown that these biomimetic surfaces lead to an increased volume fraction of bone regenerated in vivo. In the present study, we compared the distribution of cell adhesion contacts, cell spreading, and cell motility of murine bone marrow stromal cells (BMSC) on mineralized vs. nonmineralized substrates. We developed a new approach for quantification of cell-material interactions and demonstrated that cell adhesion contacts on mineralized substrates were distributed throughout the cell surface contacting the substrate, whereas on nonmineralized substrates cell adhesion contacts were present near the cell periphery. We propose that mineralized substrates stimulate the predominant expression of fibrillar contacts, and nonmineralized substrates stimulate expression of focal adhesion contacts. Cell motility assays with colloidal gold demonstrated a statistically significant decrease in the average phagokinetic index of migrating cells on mineralized vs. nonmineralized substrates after 90 min of cell seeding. We propose that the physical-chemical properties of the substrate, altered by mineralization, cause expression of specific types of cell contacts and, as a result, modify molecular mechanisms responsible for cell spreading, motility, and possibly differentiation.
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, 48109-1078, USA.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Leonova
authors.forename: Keith E
authors.initials: KE
authors.lastname: Pennington
authors.forename: Paul H
authors.initials: PH
authors.lastname: Krebsbach
authors.forename: David H
authors.initials: DH
authors.lastname: Kohn
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001854:Bone Marrow Cells / Q000166:cytology*; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000295:instrumentation*; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism; D022001:Focal Adhesions / Q000737:chemistry; D017979:Gold Colloid / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013234:Stem Cells / Q000166:cytology*
chemical_list: D001672:Biocompatible Materials; D017979:Gold Colloid; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid