title: Interplay of the physical microenvironment, contact guidance, and intracellular signaling in cell decision making.
abstract: The peritumoral physical microenvironment consists of complex topographies that influence cell migration. Cell decision making, upon encountering anisotropic, physiologically relevant physical cues, has yet to be elucidated. By integrating microfabrication with cell and molecular biology techniques, we provide a quantitative and mechanistic analysis of cell decision making in a variety of well-defined physical microenvironments. We used MDA-MB-231 breast carcinoma and HT1080 fibrosarcoma as cell models. Cell decision making after lateral confinement in 2-dimensional microcontact printed lines is governed by branch width at bifurcations. Cells confined in narrow feeder microchannels prefer to enter wider branches at bifurcations. In contrast, in feeder channels that are wider than the cell body, cells elongate along one side wall of the channel and are guided by contact with the wall to the contiguous branch channel independent of its width. Knockdown of β1-integrins or inhibition of cellular contractility suppresses contact guidance. Concurrent, but not individual, knockdown of nonmuscle myosin isoforms IIA and IIB also decreases contact guidance, which suggests the existence of a compensatory mechanism between myosin IIA and myosin IIB. Conversely, knockdown or inhibition of cell division control protein 42 homolog promotes contact guidance-mediated decision making. Taken together, the dimensionality, length scales of the physical microenvironment, and intrinsic cell signaling regulate cell decision making at intersections.-Paul, C. D., Shea, D. J., Mahoney, M. R., Chai, A., Laney, V., Hung, W.-C., Konstantopoulos, K. Interplay of the physical microenvironment, contact guidance, and intracellular signaling in cell decision making.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA; Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, Maryland, USA; and.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Paul
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA;
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Shea
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA;
authors.forename: Megan R
authors.initials: MR
authors.lastname: Mahoney
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA;
authors.forename: Andreas
authors.initials: A
authors.lastname: Chai
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA;
authors.forename: Victoria
authors.initials: V
authors.lastname: Laney
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA;
authors.forename: Wei-Chien
authors.initials: WC
authors.lastname: Hung
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland, USA; Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, Maryland, USA; and Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland, USA konstant@jhu.edu.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Konstantopoulos
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D060833:Cellular Microenvironment; D003470:Culture Media; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D044085:Microfluidics; D015398:Signal Transduction / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors
chemical_list: D003470:Culture Media; D020764:cdc42 GTP-Binding Protein
keywords: cell migration; confinement; microfluidics