title: Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence.
abstract: The relationship between the mechanical properties of cells and their molecular architecture has been the focus of extensive research for decades. The cytoskeleton, an internal polymer network, in particular determines a cell's mechanical strength and morphology. This cytoskeleton evolves during the normal differentiation of cells, is involved in many cellular functions, and is characteristically altered in many diseases, including cancer. Here we examine this hypothesized link between function and elasticity, enabling the distinction between different cells, by using a microfluidic optical stretcher, a two-beam laser trap optimized to serially deform single suspended cells by optically induced surface forces. In contrast to previous cell elasticity measurement techniques, statistically relevant numbers of single cells can be measured in rapid succession through microfluidic delivery, without any modification or contact. We find that optical deformability is sensitive enough to monitor the subtle changes during the progression of mouse fibroblasts and human breast epithelial cells from normal to cancerous and even metastatic state. The surprisingly low numbers of cells required for this distinction reflect the tight regulation of the cytoskeleton by the cell. This suggests using optical deformability as an inherent cell marker for basic cell biological investigation and diagnosis of disease.
authors.affiliation: Institute for Soft Matter Physics, Department of Physics and Geosciences, University of Leipzig, 04103 Leipzig, Germany. jguck@physik.uni-leipzig.de
authors.forename: Jochen
authors.initials: J
authors.lastname: Guck
authors.forename: Stefan
authors.initials: S
authors.lastname: Schinkinger
authors.forename: Bryan
authors.initials: B
authors.lastname: Lincoln
authors.forename: Falk
authors.initials: F
authors.lastname: Wottawah
authors.forename: Susanne
authors.initials: S
authors.lastname: Ebert
authors.forename: Maren
authors.initials: M
authors.lastname: Romeyke
authors.forename: Dominik
authors.initials: D
authors.lastname: Lenz
authors.forename: Harold M
authors.initials: HM
authors.lastname: Erickson
authors.forename: Revathi
authors.initials: R
authors.lastname: Ananthakrishnan
authors.forename: Daniel
authors.initials: D
authors.lastname: Mitchell
authors.forename: Josef
authors.initials: J
authors.lastname: Käs
authors.forename: Sydney
authors.initials: S
authors.lastname: Ulvick
authors.forename: Curt
authors.initials: C
authors.lastname: Bilby
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D048430:Cell Shape; D002471:Cell Transformation, Neoplastic; D003599:Cytoskeleton / Q000378:metabolism; D018450:Disease Progression; D004548:Elasticity; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007834:Lasers; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009362:Neoplasm Metastasis
chemical_list: D000199:Actins; D015415:Biomarkers; D014408:Biomarkers, Tumor
references.citation: J Cell Physiol. 1968 Oct;72(2):141-8
references.pmid: 4301006
references.citation: Science. 1968 Nov 29;162(3857):1024-6
references.pmid: 4301647
references.citation: J Natl Cancer Inst. 1973 Nov;51(5):1409-16
references.pmid: 4357757
references.citation: Cancer Res. 1982 Dec;42(12):5183-90
references.pmid: 7139623
references.citation: Blood. 1985 Feb;65(2):283-8
references.pmid: 3967083
references.citation: Biochim Biophys Acta. 1985;780(3):197-212
references.pmid: 3896312
references.citation: Annu Rev Biophys Biophys Chem. 1988;17:397-430
references.pmid: 3293593
references.citation: Science. 1989 Jul 14;245(4914):183-6
references.pmid: 2749255
references.citation: Cancer Res. 1990 Sep 15;50(18):6087-94
references.pmid: 1697506
references.citation: J Biomech Eng. 1990 Aug;112(3):283-94
references.pmid: 2214710
references.citation: Science. 1990 Nov 30;250(4985):1266-9
references.pmid: 2173861
references.citation: J Cell Biol. 1991 Apr;113(1):155-60
references.pmid: 2007620
references.citation: Biorheology. 1991;28(3-4):301-13
references.pmid: 1932719
references.citation: Mutat Res. 1991 Mar-Nov;256(2-6):139-48
references.pmid: 1722006
references.citation: Science. 1992 Jan 17;255(5042):325-7
references.pmid: 1549777
references.citation: Science. 1993 May 21;260(5111):1124-7
references.pmid: 7684161
references.citation: Eur J Haematol. 1994 Jan;52(1):35-41
references.pmid: 8299768
references.citation: Diagn Cytopathol. 1993 Dec;9(6):632-8
references.pmid: 8143535
references.citation: Cell Biochem Funct. 1994 Dec;12(4):267-74
references.pmid: 7834816
references.citation: Invasion Metastasis. 1994-1995;14(1-6):246-58
references.pmid: 7657517
references.citation: Obstet Gynecol Clin North Am. 1996 Sep;23(3):641-55
references.pmid: 8869950
references.citation: Science. 1998 Jan 23;279(5350):514-9
references.pmid: 9438837
references.citation: Biorheology. 1997 Jul-Oct;34(4-5):309-26
references.pmid: 9578806
references.citation: Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):921-6
references.pmid: 9927669
references.citation: Exp Cell Res. 1999 Feb 25;247(1):105-13
references.pmid: 10047452
references.citation: J Cell Sci. 1999 Apr;112 ( Pt 8):1169-79
references.pmid: 10085252
references.citation: Eur Biophys J. 1999;28(4):312-6
references.pmid: 10394623
references.citation: Phys Rev Lett. 2005 Mar 11;94(9):098103
references.pmid: 15784006
references.citation: J Can Dent Assoc. 2002 Nov;68(10):617-21
references.pmid: 12410942
references.citation: Biophys J. 1999 Dec;77(6):3085-95
references.pmid: 10585930
references.citation: J Biomech. 2000 Jan;33(1):15-22
references.pmid: 10609514
references.citation: Biophys J. 2000 Jan;78(1):520-35
references.pmid: 10620315
references.citation: Exp Cell Res. 2000 Jan 10;254(1):130-42
references.pmid: 10623473
references.citation: Science. 2000 Apr 7;288(5463):113-6
references.pmid: 10753110
references.citation: Biophys J. 2000 May;78(5):2270-9
references.pmid: 10777725
references.citation: Cancer Res. 2000 May 1;60(9):2504-11
references.pmid: 10811132
references.citation: Am J Physiol Cell Physiol. 2000 Jul;279(1):C188-94
references.pmid: 10898730
references.citation: Phys Rev Lett. 2000 Jun 5;84(23):5451-4
references.pmid: 10990966
references.citation: Phys Rev Lett. 2000 Jul 24;85(4):880-3
references.pmid: 10991422
references.citation: J Immunol Methods. 2000 Dec 1;246(1-2):175-85
references.pmid: 11121558
references.citation: Biophys J. 2001 Aug;81(2):767-84
references.pmid: 11463624
references.citation: Breast Cancer Res Treat. 2001 May;67(2):157-68
references.pmid: 11519864
references.citation: Anal Chem. 2002 Jun 1;74(11):2451-7
references.pmid: 12069222
references.citation: Cell Mol Life Sci. 2003 Jan;60(1):56-71
references.pmid: 12613658
references.citation: Phys Rev Lett. 2003 Sep 5;91(10):108103
references.pmid: 14525511
references.citation: Phys Rev Lett. 2003 Oct 10;91(15):158302
references.pmid: 14611506