Technical Advance: Introducing a novel metric, directionality time, to quantify human neutrophil chemotaxis as a function of matrix composition and stiffness

作者: Xian M. OˈBrien , Alex J. Loosley , Katie E. Oakley , Jay X. Tang , Jonathan S. Reichner

DOI: 10.1189/JLB.0913478

关键词: ChemotaxisStiffnessIntegrinDirectionalityMechanosensitive channelsBiophysicsMatrix compositionβ2 integrinBiologyHuman neutrophilImmunology

摘要: A direct consequence of cellular movement and navigation, migration incorporates elements speed, direction, persistence motion. Current techniques to parameterize the trajectory a chemotaxing cell most commonly pair speed with some measure by calculating MSD, RMS TAD, and/or CI. We address inherent limitations in TAD CI for comparative analysis introducing two new analytical tools quantify persistence: directionality index time. With use these tools, we show that mechanical properties underlying substrate contribute significantly regulation human neutrophil chemotaxis toward fMLP on Fgn-, Col-, Fn-coated gels varying elasticity. The β1-integrin ligand Col demonstrated mechanosensitive speed. In contrast, β2-integrin Fgn supported persistence. Fn, recognized β1 β2 integrins, mechanoregulated Blocking integrins cells migrating Fn identified an β2-integrin-directed modulation These data demonstrate individual components chemotactic response integrin dependence are finely tunable different ligand, mechanotactic, cues, underscoring need sensitive methods.

参考文章(21)
Takeo Matsumoto, Hironobu Abe, Toshiro Ohashi, Yoko Kato, Masaaki Sato, Local elastic modulus of atherosclerotic lesions of rabbit thoracic aortas measured by pipette aspiration method Physiological Measurement. ,vol. 23, pp. 635- 648 ,(2002) , 10.1088/0967-3334/23/4/304
R. J. Pelham, Y.-l. Wang, Cell locomotion and focal adhesions are regulated by substrate flexibility Proceedings of the National Academy of Sciences of the United States of America. ,vol. 94, pp. 13661- 13665 ,(1997) , 10.1073/PNAS.94.25.13661
Adam Engler, Lucie Bacakova, Cynthia Newman, Alina Hategan, Maureen Griffin, Dennis Discher, Substrate Compliance versus Ligand Density in Cell on Gel Responses Biophysical Journal. ,vol. 86, pp. 617- 628 ,(2004) , 10.1016/S0006-3495(04)74140-5
Alexia L. McKnight, Jennifer L. Kugel, Phillip J. Rossman, Armando Manduca, Lynn C. Hartmann, Richard L. Ehman, MR Elastography of Breast Cancer: Preliminary Results American Journal of Roentgenology. ,vol. 178, pp. 1411- 1417 ,(2002) , 10.2214/AJR.178.6.1781411
Risat A Jannat, Gregory P Robbins, Brendon G Ricart, Micah Dembo, Daniel A Hammer, Neutrophil adhesion and chemotaxis depend on substrate mechanics. Journal of Physics: Condensed Matter. ,vol. 22, pp. 194117- 194117 ,(2010) , 10.1088/0953-8984/22/19/194117
Julie B. Litzenberger, Jae-Beom Kim, Padmaja Tummala, Christopher R. Jacobs, β1 Integrins Mediate Mechanosensitive Signaling Pathways in Osteocytes Calcified Tissue International. ,vol. 86, pp. 325- 332 ,(2010) , 10.1007/S00223-010-9343-6
Chun-Min Lo, Hong-Bei Wang, Micah Dembo, Yu-li Wang, Cell Movement Is Guided by the Rigidity of the Substrate Biophysical Journal. ,vol. 79, pp. 144- 152 ,(2000) , 10.1016/S0006-3495(00)76279-5
Kaustabh Ghosh, Zhi Pan, E Guan, Shouren Ge, Yajie Liu, Toshio Nakamura, Xiang-Dong Ren, Miriam Rafailovich, Richard A.F. Clark, Cell adaptation to a physiologically relevant ECM mimic with different viscoelastic properties Biomaterials. ,vol. 28, pp. 671- 679 ,(2007) , 10.1016/J.BIOMATERIALS.2006.09.038
Tanya N. Mayadas, Xavier Cullere, Neutrophil β2 integrins: moderators of life or death decisions Trends in Immunology. ,vol. 26, pp. 388- 395 ,(2005) , 10.1016/J.IT.2005.05.002