title: Multiscale computational models of complex biological systems.
abstract: Integration of data across spatial, temporal, and functional scales is a primary focus of biomedical engineering efforts. The advent of powerful computing platforms, coupled with quantitative data from high-throughput experimental methodologies, has allowed multiscale modeling to expand as a means to more comprehensively investigate biological phenomena in experimentally relevant ways. This review aims to highlight recently published multiscale models of biological systems, using their successes to propose the best practices for future model development. We demonstrate that coupling continuous and discrete systems best captures biological information across spatial scales by selecting modeling techniques that are suited to the task. Further, we suggest how to leverage these multiscale models to gain insight into biological systems using quantitative biomedical engineering methods to analyze data in nonintuitive ways. These topics are discussed with a focus on the future of the field, current challenges encountered, and opportunities yet to be realized.
authors: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
authors: Joseph
authors: J
authors: Walpole
authors: Jason A
authors: JA
authors: Papin
authors: Shayn M
authors: SM
authors: Peirce
mesh_terms: D000818:Animals; D001698:Biomedical Engineering / Q000379:methods; D019295:Computational Biology / Q000379:methods; D006801:Humans; D008954:Models, Biological; D012107:Research Design; D015398:Signal Transduction; D049490:Systems Biology; D013816:Thermodynamics; D023822:Tissue Engineering / Q000379:methods
references: Curr Top Dev Biol. 2008;81:311-40
references: 18023733
references: Curr Top Dev Biol. 2008;81:435-60
references: 18023737
references: Front Physiol. 2012 Jun 06;3:170
references: 22685435
references: J Biomech Eng. 2009 Oct;131(10):101006
references: 19831476
references: J Theor Biol. 2010 Aug 7;265(3):433-42
references: 20447409
references: Biomed Sci Instrum. 2012;48:423-30
references: 22846315
references: Philos Trans A Math Phys Eng Sci. 2009 Sep 13;367(1902):3585-606
references: 19657012
references: J Theor Biol. 2010 Jun 7;264(3):838-46
references: 20307549
references: Physiol Genomics. 2011 Aug 24;43(16):951-64
references: 21673075
references: Nat Rev Genet. 2007 May;8(5):331-40
references: 17440530
references: J Theor Biol. 2011 Mar 7;272(1):55-63
references: 21167179
references: Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9185-90
references: 22615376
references: Nat Med. 2009 Nov;15(11):1298-306
references: 19881493
references: Biophys J. 2003 Oct;85(4):2273-86
references: 14507692
references: J Biomech. 2011 Nov 10;44(16):2795-801
references: 21945569
references: PLoS One. 2009 Oct 16;4(10):e7190
references: 19834621
references: Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:5452-5
references: 19964679
references: Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5850-5
references: 22454498
references: Theor Biol Med Model. 2011 Jan 19;8:1
references: 21247471
references: PLoS One. 2010 Jan 14;5(1):e8511
references: 20076760
references: Crit Rev Biomed Eng. 2010;38(3):225-54
references: 21133835
references: Front Physiol. 2011 Aug 11;2:43
references: 21886622
references: Tissue Eng Part A. 2011 Sep;17(17-18):2133-41
references: 21513462
references: Theor Biol Med Model. 2011 Apr 04;8:6
references: 21463529
references: Front Physiol. 2011 Oct 04;2:62
references: 22007175
references: Philos Trans A Math Phys Eng Sci. 2010 Jun 28;368(1921):2937-60
references: 20478915
references: J Immunol. 2012 Apr 1;188(7):3169-78
references: 22379032
references: Microcirculation. 2009 Feb;16(2):115-30
references: 19023690
references: Nat Biotechnol. 2012 Aug;30(8):792-7
references: 22820316
references: Proc Natl Acad Sci U S A. 2010 Jun 1;107(22):10092-6
references: 20479267
references: Sci Transl Med. 2011 Aug 31;3(98):98ra83
references: 21885405
references: Front Physiol. 2011 Feb 24;2:4
references: 21483730
references: PLoS One. 2009 Dec 31;4(12):e8515
references: 20046881
references: Methods Enzymol. 2011;500:411-33
references: 21943909
references: BMC Syst Biol. 2011 Aug 16;5:130
references: 21846360
references: BMC Syst Biol. 2009 Jul 28;3:78
references: 19638230
references: J Comput Biol. 2011 Feb;18(2):169-82
references: 21314456
references: J Gen Physiol. 2010 Jun;135(6):575-81
references: 20513759
references: IEEE Signal Process Mag. 2008 Mar;25(2):121-144
references: 20689655
references: PLoS Comput Biol. 2009 Dec;5(12):e1000612
references: 20019797
references: IEEE Trans Biomed Eng. 2011 Oct;58(10):3024-7
references: 21708496
references: Dev Biol. 2004 Jul 1;271(1):210-22
references: 15196962
references: J Theor Biol. 2008 Jan 7;250(1):25-36
references: 18028963
references: HFSP J. 2010 Jun;4(3-4):142-52
references: 21119766
references: BMC Syst Biol. 2011 May 02;5:59
references: 21535871
references: Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15522-7
references: 21876160
references: Ann Biomed Eng. 2007 Jun;35(6):916-36
references: 17436112
references: PLoS Comput Biol. 2010 Oct 28;6(10):e1000970
references: 21060853
references: Biophys J. 2009 Apr 22;96(8):2989-3004
references: 19383446
references: Prog Biophys Mol Biol. 2011 Oct;107(1):21-31
references: 21704063
references: Pharm Res. 2011 Dec;28(12):2996-3015
references: 22033880
references: Ann Biomed Eng. 2011 Nov;39(11):2669-82
references: 21809144
references: J Cell Biol. 2010 Jan 11;188(1):11-9
references: 19951899
references: J Exp Zool. 2002 Oct 15;294(3):216-51
references: 12362430
references: Open Pacing Electrophysiol Ther J. 2010;3:66-74
references: 22919435
references: PLoS Comput Biol. 2009 Jan;5(1):e1000260
references: 19132078
references: PLoS One. 2011;6(8):e23795
references: 21901136
references: Circ Res. 2011 Jan 7;108(1):70-84
references: 21212390
references: PLoS Comput Biol. 2011 Dec;7(12):e1002270
references: 22144878
references: Biomech Model Mechanobiol. 2012 Mar;11(3-4):363-77
references: 21626394
references: Prog Biophys Mol Biol. 2011 Oct;107(1):147-55
references: 21763714
references: N Engl J Med. 2004 Jan 1;350(1):48-58
references: 14702427
references: Nature. 2000 Jul 13;406(6792):188-92
references: 10910359
references: Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17675-80
references: 19805118
references: Front Physiol. 2011 May 09;2:20
references: 21720536
references: Prog Biophys Mol Biol. 2012 Oct-Nov;110(2-3):295-304
references: 22841534
references: Math Biosci. 2011 Jun;231(2):186-96
references: 21385589