title: Microfluidics as a functional tool for cell mechanics.
abstract: Living cells are a fascinating demonstration of nature's most intricate and well-coordinated micromechanical objects. They crawl, spread, contract, and relax-thus performing a multitude of complex mechanical functions. Alternatively, they also respond to physical and chemical cues that lead to remodeling of the cytoskeleton. To understand this intricate coupling between mechanical properties, mechanical function and force-induced biochemical signaling requires tools that are capable of both controlling and manipulating the cell microenvironment and measuring the resulting mechanical response. In this review, the power of microfluidics as a functional tool for research in cell mechanics is highlighted. In particular, current literature is discussed to show that microfluidics powered by soft lithographic techniques offers the following capabilities that are of significance for understanding the mechanical behavior of cells: (i) Microfluidics enables the creation of in vitro models of physiological environments in which cell mechanics can be probed. (ii) Microfluidics is an excellent means to deliver physical cues that affect cell mechanics, such as cell shape, fluid flow, substrate topography, and stiffness. (iii) Microfluidics can also expose cells to chemical cues, such as growth factors and drugs, which alter their mechanical behavior. Moreover, these chemical cues can be delivered either at the whole cell or subcellular level. (iv) Microfluidic devices offer the possibility of measuring the intrinsic mechanical properties of cells in a high throughput fashion. (v) Finally, microfluidic methods provide exquisite control over drop size, generation, and manipulation. As a result, droplets are being increasingly used to control the physicochemical environment of cells and as biomimetic analogs of living cells. These powerful attributes of microfluidics should further stimulate novel means of investigating the link between physicochemical cues and the biomechanical response of cells. Insights from such studies will have implications in areas such as drug delivery, medicine, tissue engineering, and biomedical diagnostics.
authors.forename: Siva A
authors.initials: SA
authors.lastname: Vanapalli
authors.forename: Michel H G
authors.initials: MH
authors.lastname: Duits
authors.forename: Frieder
authors.initials: F
authors.lastname: Mugele
references.citation: Biophys J. 2001 Aug;81(2):767-84
references.pmid: 11463624
references.citation: Lab Chip. 2007 May;7(5):647-9
references.pmid: 17476388
references.citation: Anal Chem. 2005 Jul 1;77(13):3993-9
references.pmid: 15987102
references.citation: Lab Chip. 2008 Apr;8(4):519-26
references.pmid: 18369505
references.citation: Electrophoresis. 2006 Dec;27(24):5073-80
references.pmid: 17124709
references.citation: Pflugers Arch. 2008 Apr;456(1):13-27
references.pmid: 18213477
references.citation: J Am Chem Soc. 2003 Nov 26;125(47):14613-9
references.pmid: 14624612
references.citation: Lab Chip. 2008 Jul;8(7):1062-70
references.pmid: 18584080
references.citation: Science. 2005 Nov 18;310(5751):1139-43
references.pmid: 16293750
references.citation: Biorheology. 1982;19(6):737-53
references.pmid: 7184522
references.citation: Lab Chip. 2008 Feb;8(2):198-220
references.pmid: 18231657
references.citation: Lab Chip. 2005 Jan;5(1):14-9
references.pmid: 15616734
references.citation: Nat Biotechnol. 2005 Mar;23(3):361-5
references.pmid: 15723045
references.citation: Nature. 2001 Apr 19;410(6831):905-8
references.pmid: 11309609
references.citation: Anal Chem. 2005 Feb 1;77(3):785-96
references.pmid: 15679345
references.citation: Acta Biomater. 2007 Jul;3(4):413-38
references.pmid: 17540628
references.citation: Nat Rev Mol Cell Biol. 2006 Mar;7(3):211-24
references.pmid: 16496023
references.citation: Lab Chip. 2009 Apr 7;9(7):982-90
references.pmid: 19294311
references.citation: Lab Chip. 2007 Feb;7(2):264-72
references.pmid: 17268630
references.citation: Ann Med. 2003;35(8):564-77
references.pmid: 14708967
references.citation: Microcirculation. 2000 Dec;7(6 Pt 1):419-27
references.pmid: 11142339
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 4;105(9):3191-6
references.pmid: 18316742
references.citation: Ann Biomed Eng. 2004 Apr;32(4):520-30
references.pmid: 15117025
references.citation: Nat Cell Biol. 2001 May;3(5):466-72
references.pmid: 11331874
references.citation: Langmuir. 2008 May 6;24(9):4439-42
references.pmid: 18361535
references.citation: Science. 2003 May 9;300(5621):955-8
references.pmid: 12738857
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14010-5
references.pmid: 16172382
references.citation: Biomed Microdevices. 2004 Dec;6(4):269-78
references.pmid: 15548874
references.citation: Biophys J. 2003 Jan;84(1):623-33
references.pmid: 12524315
references.citation: J Biomech Eng. 1990 Aug;112(3):277-82
references.pmid: 2214709
references.citation: Nat Mater. 2003 Nov;2(11):715-25
references.pmid: 14593396
references.citation: Ann Biomed Eng. 2006 Jan;34(1):102-13
references.pmid: 16456640
references.citation: Lab Chip. 2006 Jan;6(1):149-54
references.pmid: 16372083
references.citation: Lab Chip. 2005 Oct;5(10):1089-95
references.pmid: 16175265
references.citation: J Biochem Biophys Methods. 2001 Dec 4;50(1):15-27
references.pmid: 11714508
references.citation: Nat Biotechnol. 2008 Jan;26(1):120-6
references.pmid: 18026090
references.citation: Angew Chem Int Ed Engl. 2006 Nov 13;45(44):7336-56
references.pmid: 17086584
references.citation: Nature. 2007 May 31;447(7144):592-5
references.pmid: 17538621
references.citation: Physiol Rev. 2001 Apr;81(2):685-740
references.pmid: 11274342
references.citation: Biophys J. 2005 May;88(5):3689-98
references.pmid: 15722433
references.citation: Langmuir. 2008 Jun 3;24(11):5955-60
references.pmid: 18471001
references.citation: Anal Sci. 2007 Mar;23(3):261-6
references.pmid: 17372365
references.citation: Science. 1993 May 21;260(5111):1124-7
references.pmid: 7684161
references.citation: Lab Chip. 2008 Aug;8(8):1292-9
references.pmid: 18651071
references.citation: Med Eng Phys. 2005 Mar;27(2):157-65
references.pmid: 15642511
references.citation: Science. 2000 Apr 7;288(5463):113-6
references.pmid: 10753110
references.citation: J Biomech Eng. 1987 May;109(2):103-9
references.pmid: 3599933
references.citation: Lab Chip. 2008 May;8(5):660-2
references.pmid: 18432333
references.citation: Cell. 2003 Feb 21;112(4):453-65
references.pmid: 12600310
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1484-9
references.pmid: 12552122
references.citation: Nat Mater. 2005 Jul;4(7):557-61
references.pmid: 15937489
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20496-500
references.pmid: 18077341
references.citation: J Biomech. 2007;40(9):2088-95
references.pmid: 17188279
references.citation: Methods Cell Biol. 2007;83:443-72
references.pmid: 17613320
references.citation: J Biomech. 2005 Oct;38(10):1949-71
references.pmid: 16084198
references.citation: Biomaterials. 2007 Oct;28(28):4098-104
references.pmid: 17588654
references.citation: Biorheology. 1998 Jul-Oct;35(4-5):245-61
references.pmid: 10474653
references.citation: Nature. 2001 Sep 13;413(6852):194-202
references.pmid: 11557988
references.citation: Annu Rev Physiol. 1992;54:135-52
references.pmid: 1373277
references.citation: Trends Biotechnol. 2007 Mar;25(3):111-8
references.pmid: 17257698
references.citation: Annu Rev Biomed Eng. 2000;2:189-226
references.pmid: 11701511
references.citation: J Immunol Methods. 2003 Feb;273(1-2):53-62
references.pmid: 12535797
references.citation: Anal Chem. 2002 Aug 15;74(16):3984-90
references.pmid: 12199564
references.citation: Cell. 2006 Aug 25;126(4):677-89
references.pmid: 16923388
references.citation: Anal Chem. 2005 Mar 15;77(6):1539-44
references.pmid: 15762555
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10259-10264
references.pmid: 16793927
references.citation: Anal Chem. 2008 Oct 1;80(19):7543-8
references.pmid: 18729474
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9274-9
references.pmid: 12883003
references.citation: Lab Chip. 2007 Apr;7(4):516-9
references.pmid: 17389970
references.citation: Anal Chem. 2004 Aug 15;76(16):4715-20
references.pmid: 15307781
references.citation: Biotechnol Bioeng. 2005 Jan 5;89(1):1-8
references.pmid: 15580587
references.citation: Anal Chem. 2006 May 15;78(10):3472-7
references.pmid: 16689552
references.citation: Nat Nanotechnol. 2007 Dec;2(12):780-3
references.pmid: 18654431
references.citation: Lab Chip. 2008 Oct;8(10):1632-9
references.pmid: 18813384
references.citation: Ultrasound Med Biol. 2007 Jan;33(1):145-51
references.pmid: 17189057
references.citation: Lab Chip. 2008 Aug;8(8):1262-4
references.pmid: 18651066
references.citation: Biomed Microdevices. 2004 Dec;6(4):325-39
references.pmid: 15548879
references.citation: Nature. 2006 Jul 27;442(7101):403-11
references.pmid: 16871208
references.citation: Biotechnol Bioeng. 2008 May 1;100(1):150-8
references.pmid: 18078299
references.citation: Blood. 1984 Jan;63(1):73-82
references.pmid: 6689955
references.citation: Lab Chip. 2009 May 21;9(10):1461-7
references.pmid: 19417915
references.citation: Nature. 2006 Jul 27;442(7101):368-73
references.pmid: 16871203
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2390-5
references.pmid: 15695588
references.citation: Langmuir. 2009 Jul 7;25(13):7743-51
references.pmid: 19219968
references.citation: Anal Chem. 2008 Oct 15;80(20):7714-9
references.pmid: 18798650
references.citation: Anal Chem. 2007 Nov 15;79(22):8557-63
references.pmid: 17953452
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14553-8
references.pmid: 17804810
references.citation: Cell Microbiol. 2008 Oct;10(10):1968-74
references.pmid: 18754851
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14618-22
references.pmid: 14638939
references.citation: Anal Chem. 1998 Dec 1;70(23):4974-84
references.pmid: 21644679
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):538-42
references.pmid: 16407104
references.citation: Lab Chip. 2006 Apr;6(4):567-74
references.pmid: 16572221
references.citation: Biophys J. 2007 Dec 15;93(12):4453-61
references.pmid: 18045965
references.citation: J Cell Sci. 2003 Apr 15;116(Pt 8):1397-408
references.pmid: 12640025
references.citation: Biomaterials. 1999 Dec;20(23-24):2363-76
references.pmid: 10614942
references.citation: Lab Chip. 2007 Dec;7(12):1759-66
references.pmid: 18030398
references.citation: Nat Biotechnol. 2005 Jan;23(1):83-7
references.pmid: 15608628
references.citation: Langmuir. 2004 Dec 21;20(26):11684-91
references.pmid: 15595798
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):18886-91
references.pmid: 18006663
references.citation: Analyst. 2004 Nov;129(11):1026-31
references.pmid: 15508030
references.citation: Nature. 2001 Jun 28;411(6841):1016
references.pmid: 11429594
references.citation: Lab Chip. 2007 Apr;7(4):448-56
references.pmid: 17389960
references.citation: FASEB J. 1991 Apr;5(7):2013-9
references.pmid: 1707019
references.citation: Lab Chip. 2007 Jun;7(6):681-94
references.pmid: 17538709
references.citation: Science. 2002 Jan 25;295(5555):647-51
references.pmid: 11809963
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15861-6
references.pmid: 15514025
references.citation: Curr Opin Cell Biol. 2007 Feb;19(1):101-7
references.pmid: 17174543
references.citation: Physiol Rev. 1995 Jul;75(3):519-60
references.pmid: 7624393
references.citation: Biomed Microdevices. 2008 Oct;10(5):727-37
references.pmid: 18523888