title: Mimicking white matter tract topography using core-shell electrospun nanofibers to examine migration of malignant brain tumors.
abstract: Glioblastoma multiforme (GBM), one of the deadliest forms of human cancer, is characterized by its high infiltration capacity, partially regulated by the neural extracellular matrix (ECM). A major limitation in developing effective treatments is the lack of in vitro models that mimic features of GBM migration highways. Ideally, these models would permit tunable control of mechanics and chemistry to allow the unique role of each of these components to be examined. To address this need, we developed aligned nanofiber biomaterials via core-shell electrospinning that permit systematic study of mechanical and chemical influences on cell adhesion and migration. These models mimic the topography of white matter tracts, a major GBM migration 'highway'. To independently investigate the influence of chemistry and mechanics on GBM behaviors, nanofiber mechanics were modulated by using different polymers (i.e., gelatin, poly(ethersulfone), poly(dimethylsiloxane)) in the 'core' while employing a common poly(ε-caprolactone) (PCL) 'shell' to conserve surface chemistry. These materials revealed GBM sensitivity to nanofiber mechanics, with single cell morphology (Feret diameter), migration speed, focal adhesion kinase (FAK) and myosin light chain 2 (MLC2) expression all showing a strong dependence on nanofiber modulus. Similarly, modulating nanofiber chemistry using extracellular matrix molecules (i.e., hyaluronic acid (HA), collagen, and Matrigel) in the 'shell' material with a common PCL 'core' to conserve mechanical properties revealed GBM sensitivity to HA; specifically, a negative effect on migration. This system, which mimics the topographical features of white matter tracts, should allow further examination of the complex interplay of mechanics, chemistry, and topography in regulating brain tumor behaviors.
authors.affiliation: William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Shreyas S
authors.initials: SS
authors.lastname: Rao
authors.forename: Mark T
authors.initials: MT
authors.lastname: Nelson
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Xue
authors.forename: Jessica K
authors.initials: JK
authors.lastname: DeJesus
authors.forename: Mariano S
authors.initials: MS
authors.lastname: Viapiano
authors.forename: John J
authors.initials: JJ
authors.lastname: Lannutti
authors.forename: Atom
authors.initials: A
authors.lastname: Sarkar
authors.forename: Jessica O
authors.initials: JO
authors.lastname: Winter
mesh_terms: D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D024722:Cardiac Myosins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D055595:Mechanical Phenomena / Q000187:drug effects; D018994:Myosin Light Chains / Q000378:metabolism; D057139:Nanofibers / Q000737:chemistry* / Q000648:ultrastructure; D011091:Polyesters / Q000494:pharmacology
chemical_list: D004129:Dimethylpolysiloxanes; D018994:Myosin Light Chains; D011091:Polyesters; C107184:myosin light chain 2; C016240:polycaprolactone; D051416:Focal Adhesion Protein-Tyrosine Kinases; D024722:Cardiac Myosins