title: Heterogeneous elastic response of human lung microvascular endothelial cells to barrier modulating stimuli.
abstract: In this study we employ atomic force microscopy, supported by finite element analysis and fluorescence microscopy, to characterize the elastic properties accompanying cytoskeletal structural rearrangements of lung microvascular endothelial cells in response to barrier altering stimuli. Statistical analysis of elasticity data obtained from multiple cells demonstrates a heterogeneous cellular elastic response to barrier-enhancing and barrier-disrupting agents; sphingosine 1-phosphate (S1P) and thrombin, respectively. A small but detectable (10%) increase in the average elastic modulus of all cells is observed for S1P, which is accompanied by a corresponding significant decrease in cell thickness. Variable effects of thrombin on these parameters were observed. To account for possible substrate effects in our elasticity analysis, we analyzed only the low-force sections of the force-displacement curves and utilized a finite-thickness correction to the Hertzian model. Our finite element analysis results substantiate this approach. The heterogeneous elastic behavior correlates with differential cytoskeletal rearrangements observed with fluorescence microscopy.
  
  
  BACKGROUND
  This team of investigators employed atomic force microscopy coupled with finite element analysis and fluorescence microscopy to characterize the elastic properties accompanying cytoskeletal structural rearrangements of lung microvascular endothelial cells in response to barrier altering stimuli, demonstrating the validity of their approach.
authors.affiliation: Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, California, USA; Bioengineering Departments, University of California San Diego, La Jolla, California, USA. Electronic address: ftarce@ucsd.edu.
authors.forename: Fernando Terán
authors.initials: FT
authors.lastname: Arce
authors.forename: Brian
authors.initials: B
authors.lastname: Meckes
authors.forename: Sara M
authors.initials: SM
authors.lastname: Camp
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dudek
authors.forename: Ratnesh
authors.initials: R
authors.lastname: Lal
mesh_terms: D000199:Actins / Q000378:metabolism; D002460:Cell Line; D003599:Cytoskeleton; D004548:Elasticity / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D020342:Finite Element Analysis; D006801:Humans; D008168:Lung / Q000166:cytology*; D008246:Lysophospholipids / Q000494:pharmacology*; D055806:Microvessels / Q000166:cytology*; D008954:Models, Biological; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013314:Stress, Mechanical; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D000199:Actins; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013917:Thrombin; D013110:Sphingosine
keywords: AFM; Cell; Elasticity; F-actin; FEM