Engineering cellular response using nanopatterned bulk metallic glass.
Nanopatterning of biomaterials is rapidly emerging as a tool to engineer cell function. Bulk metallic glasses (BMGs), a class of biocompatible materials, are uniquely suited to study nanopattern-cell interactions as they allow for versatile fabrication of nanopatterns through thermoplastic forming. Work presented here employs nanopatterned BMG substrates to explore detection of nanopattern feature sizes by various cell types, including cells that are associated with foreign body response, pathology, and tissue repair. Fibroblasts decreased in cell area as the nanopattern feature size increased, and fibroblasts could detect nanopatterns as small as 55 nm in size. Macrophages failed to detect nanopatterns of 150 nm or smaller in size, but responded to a feature size of 200 nm, resulting in larger and more elongated cell morphology. Endothelial cells responded to nanopatterns of 100 nm or larger in size by a significant decrease in cell size and elongation. On the basis of these observations, nondimensional analysis was employed to correlate cellular morphology and substrate nanotopography. Analysis of the molecular pathways that induce cytoskeletal remodeling, in conjunction with quantifying cell traction forces with nanoscale precision using a unique FIB-SEM technique, enabled the characterization of underlying biomechanical cues. Nanopatterns altered serum protein adsorption and effective substrate stiffness, leading to changes in focal adhesion density and compromised activation of Rho-A GTPase in fibroblasts. As a consequence, cells displayed restricted cell spreading and decreased collagen production. These observations suggest that topography on the nanoscale can be designed to engineer cellular responses to biomaterials.
Center for Research on Interface Structures and Phenomena, Yale University , New Haven, Connecticut 06520, United States.
Jagannath
J
Padmanabhan
Emily R
ER
Kinser
Mark A
MA
Stalter
Christopher
C
Duncan-Lewis
Jenna L
JL
Balestrini
Andrew J
AJ
Sawyer
Jan
J
Schroers
Themis R
TR
Kyriakides
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry; D005549:Foreign-Body Reaction; D020558:GTP Phosphohydrolases / Q000737:chemistry; D005898:Glass / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008670:Metals / Q000737:chemistry*; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D049329:Nanostructures / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D015202:Protein Engineering; D020742:rhoA GTP-Binding Protein / Q000737:chemistry
D001672:Biocompatible Materials; D005353:Fibronectins; D008670:Metals; C066737:RHOA protein, human; D003094:Collagen; D020558:GTP Phosphohydrolases; D020742:rhoA GTP-Binding Protein