title: A linear programming approach to reconstructing subcellular structures from confocal images for automated generation of representative 3D cellular models.
abstract: This paper presents a novel computer vision algorithm to analyze 3D stacks of confocal images of fluorescently stained single cells. The goal of the algorithm is to create representative in silico model structures that can be imported into finite element analysis software for mechanical characterization. Segmentation of cell and nucleus boundaries is accomplished via standard thresholding methods. Using novel linear programming methods, a representative actin stress fiber network is generated by computing a linear superposition of fibers having minimum discrepancy compared with an experimental 3D confocal image. Qualitative validation is performed through analysis of seven 3D confocal image stacks of adherent vascular smooth muscle cells (VSMCs) grown in 2D culture. The presented method is able to automatically generate 3D geometries of the cell's boundary, nucleus, and representative F-actin network based on standard cell microscopy data. These geometries can be used for direct importation and implementation in structural finite element models for analysis of the mechanics of a single cell to potentially speed discoveries in the fields of regenerative medicine, mechanobiology, and drug discovery.
authors: Department of Bioengineering, Clemson University, Clemson, SC 29634-0905, USA. stwood@clemson.edu
authors: Scott T
authors: ST
authors: Wood
authors: Brian C
authors: BC
authors: Dean
authors: Delphine
authors: D
authors: Dean
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D018613:Microscopy, Confocal / Q000379:methods*; D008954:Models, Biological; D010363:Pattern Recognition, Automated / Q000379:methods*; D011382:Programming, Linear; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013347:Subcellular Fractions / Q000648:ultrastructure*
references: Science. 2007 Jan 19;315(5810):370-3
references: 17234946
references: JAMA. 2011 May 25;305(20):2110-1
references: 21610244
references: Biochem Biophys Res Commun. 2005 Aug 19;334(1):183-92
references: 15992772
references: J Nanobiotechnology. 2006 Oct 20;4:10
references: 17054792
references: Cytometry A. 2005;63(1):20-33
references: 15584021
references: Cytometry A. 2003 Nov;56(1):23-36
references: 14566936
references: J Biomech. 2010 Jun 18;43(9):1806-16
references: 20188374
references: Respir Physiol Neurobiol. 2008 Nov 30;163(1-3):25-32
references: 18395498
references: Biophys J. 2008 Apr 15;94(8):2955-64
references: 18055529
references: Biophys J. 2009 Apr 22;96(8):3379-89
references: 19383481
references: Curr Opin Cell Biol. 2007 Feb;19(1):101-7
references: 17174543
references: J Microsc. 2008 Jul;231(Pt 1):105-14
references: 18638194
references: Acta Biomater. 2007 Jul;3(4):413-38
references: 17540628
references: J Appl Physiol (1985). 2009 Jan;106(1):221-32
references: 19008489
references: Ann Med. 2003;35(8):564-77
references: 14708967
references: Cell Mol Bioeng. 2009 Dec 1;2(4):475-485
references: 20376295
references: J Cell Sci. 2003 Apr 1;116(Pt 7):1157-73
references: 12615960
references: J Biomech Eng. 2009 Apr;131(4):041001
references: 19275430
references: Curr Opin Genet Dev. 2004 Aug;14(4):399-406
references: 15261656
references: Perspect Biol Med. 2010 Summer;53(3):407-24
references: 20639608
references: Phys Rev E Stat Nonlin Soft Matter Phys. 2010 Feb;81(2 Pt 1):021924
references: 20365612
references: Nat Mater. 2006 Aug;5(8):636-40
references: 16845421
references: J Biomech. 2005 Aug;38(8):1685-93
references: 15958226
references: J Biomech. 2010 Jan 5;43(1):23-30
references: 19815217
references: Biophys J. 2003 Nov;85(5):3336-49
references: 14581235
references: Nat Mater. 2005 Jul;4(7):557-61
references: 15937489
references: J Biomech Eng. 2007 Jun;129(3):315-23
references: 17536898
references: J Biomech. 2008;41(8):1722-9
references: 18433758
references: Nature. 2007 Jan 18;445(7125):295-8
references: 17230186
references: Nature. 2003 Apr 17;422(6933):741-5
references: 12700767
references: J Cell Sci. 2003 Apr 15;116(Pt 8):1397-408
references: 12640025
references: J Biomech. 2010 Jul 20;43(10):1941-6
references: 20382389
references: Cell Motil Cytoskeleton. 2007 Jul;64(7):509-18
references: 17342763
references: J Biomech. 2005 Aug;38(8):1728-32
references: 15958232