Mechanomics: an emerging field between biology and biomechanics

Abstract

Cells sense various in vivo mechanical stimuli, which initiate downstream signaling to mechanical forces. While a body of evidences is presented on the impact of limited mechanical regulators in past decades, the mechanisms how biomechanical responses globally affect cell function need to be addressed. Complexity and diversity of in vivo mechanical clues present distinct patterns of shear flow, tensile stretch, or mechanical compression with various parametric combination of its magnitude, duration, or frequency. Thus, it is required to understand, from the viewpoint of mechanobiology, what mechanical features of cells are, why mechanical properties are different among distinct cell types, and how forces are transduced to downstream biochemical signals. Meanwhile, those in vitro isolated mechanical stimuli are usually coupled together in vivo, suggesting that the different factors that are in effect individually could be canceled out or orchestrated with each other. Evidently, omics analysis, a powerful tool in the field of system biology, is advantageous to combine with mechanobiology and then to map the fullset of mechanically sensitive proteins and transcripts encoded by its genome. This new emerging field, namely mechanomics, makes it possible to elucidate the global responses under systematically-varied mechanical stimuli. This review discusses the current advances in the related fields of mechanomics and elaborates how cells sense external forces and activate the biological responses.

Keywords

mechanomics / mechanobiology / proteomics / transcriptomics

References

[1] Angele P, Schumann D, Angele M, Kinner B, Englert C, Hente R, Fuchtmeier B, Nerlich M, Neumann C, Kujat R (2004) Cyclic, mechanical compression enhances chondrogenesis of mesenchymal progenitor cells in tissue engineering scaffolds. Biorheology41: 335-346

[2] Arnsdorf EJ, Tummala P, Kwon RY, Jacobs CR (2009) Mechanically induced osteogenic differentiation—the role of RhoA, ROCKII and cytoskeletal dynamics. J Cell Sci122: 546-553

[3] Baba K, Asada T, Hayashi T (2000) Relation between developmental changes on anatomical structure and on protein pattern in differentiating xylem of tension wood. J Wood Sci46: 1-7

[4] Barakat AI, Lieu DK (2003) Differential responsiveness of vascular endothelial cells to different types of fluid mechanical shear stress. Cell Biochem Biophys<?Pub Caret?>38: 323-343

[5] Biggs MJP, Richards RG, McFarlane S, Wilkinson CDW, Oreffo ROC, Dalby MJ (2008) Adhesion formation of primary human osteoblasts and the functional response of mesenchymal stem cells to 330 nm deep microgrooves. J R Soc Interface5: 1231-1242

[6] Bonassar LJ, Grodzinsky AJ, Frank EH, Davila SG, Bhaktav NR, Trippel SB (2001) The effect of dynamic compression on the response of articular cartilage to insulin-like growth factor-I. J Orthop Res19: 11-17

[7] Brooks AR, Lelkes PI, Rubanyi GM (2002) Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol Genomics9: 27-41

[8] Carey SP, D’Alfonso TM, Shin SJ, Reinhart-King CA (2012) Mechanobiology of tumor invasion: engineering meets oncology. Crit Rev Oncol Hematol83: 170-183

[9] Carter DR, Beaupre GS, Giori NJ, Helms JA (1998) Mechanobiology of skeletal regeneration. Clin Orthop355: S41-S55

[10] Chaplain MAJ, Graziano L, Preziosi L (2006) Mathematical modelling of the loss of tissue compression responsiveness and its role in solid tumour development. Math Med Biol23: 197-229

[11] Chen BPC, Li YS, Zhao YH, Chen KD, Li S, Lao JM, Yuan SL, Shyy JYJ, Chien S (2001) DNA microarray analysis of gene expression in endothelial cells in response to 24-h shear stress. Physiol Genomics7: 55-63

[12] Cohen DM, Chen CS (2008) Mechanical control of stem cell differentiation. In: Bhatia S, Polak J(eds) StemBook. Harvard Stem Cell Institute, Cambridge, pp 1-16

[13] Cui YH, Huo B, Sun SJ, Yang F, Gao YX, Pan J, Long M (2011) Fluid dynamics analysis of a novel micropatterned cell bioreactor. Ann Biomed Eng39: 1592-1605

[14] Dado D, Sagi M, Levenberg S, Zemel A (2012) Mechanical control of stem cell differentiation. Regen Med7: 101-116

[15] Dalby MJ, Andar A, Nag A, Affrossman S, Tare R, McFarlane S, Oreffo ROC (2008) Genomic expression of mesenchymal stem cells to altered nanoscale topographies. J R Soc Interface5: 1055-1065

[16] Davies PF, Remuzzi A, Gordon EJ, Dewey CF, Gimbrone MA (1986) Turbulent fluid shear-stress induces vascular endothelial-cell turnover in vitro. Proc Natl Acad Sci USA83: 2114-2117

[17] Davies PF, Spaan JA, Krams R (2005) Shear stress biology of the endothelium. Ann Biomed Eng33: 1714-1718

[18] Dejardin A, Leple JC, Lesage-Descauses MC, Costa G, Pilate G (2004) Expressed sequence tags from poplar wood tissues—a comparative analysis from multiple libraries. Plant Biol6: 55-64

[19] Evans E, Yeung A (1989) Apparent viscosity and cortical tension of blood granulocytes determined by micropipet aspiration. Biophys J56: 151-160

[20] Feuerecker M, Feuerecker B, Matzel S, Long M, Strewe C, Kaufmann I, Hoerl M, Schelling G, Rehm M, Chouker A (2013) Five days of head-down-tilt bed rest induces noninflammatory shedding of L-selectin. J Appl Physiol115: 235-242

[21] Fu CL, Tong CF, Dong C, Long M (2011a) Modeling of cell aggregation dynamics governed by receptor-ligand binding under shear flow. Cell Mol Bioeng4: 427-441

[22] Fu CL, Tong CF, Wang ML, Gao YX, Zhang Y, Lu SQ, Liang SL, Dong C, Long M (2011b) Determining beta(2)-integrin and intercellular adhesion molecule 1 binding kinetics in tumor cell adhesion to leukocytes and endothelial cells by a gas-driven micropipette assay. J Biol Chem286: 34777-34787

[23] Geiger B, Spatz JP, Bershadsky AD (2009) Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol10: 21-33

[24] Grossi A, Lametsch R, Karlsson AH, Lawson MA (2011) Mechanical stimuli on C2C12 myoblasts affect myoblast differentiation, focal adhesion kinase phosphorylation and galectin-1 expression: a proteomic approach. Cell Biol Int35: 579-586

[25] Herranz R, Larkin OJ, Dijkstra CE, Hill RJ, Anthony P, Davey MR, Eaves L, van Loon JJWA, Medina FJ, Marco R (2012) Microgravity simulation by diamagnetic levitation: effects of a strong gradient magnetic field on the transcriptional profile of Drosophila melanogaster. BMC Genomics13(1): 52

[26] Heydarkhan-Hagvall S, Chien S, Nelander S, Li YC, Yuan SL, Lao JM, Haga JH, Lian I, Nguyen P, Risberg B (2006) DNA microarray study on gene expression profiles in co-cultured endothelial and smooth muscle cells in response to 4-and 24-h shear stress. Mol Cell Biochem281: 1-15

[27] Horimizu M, Kawase T, Tanaka T, Okuda K, Nagata M, Burns DM, Yoshie H (2013) Biomechanical evaluation by AFM of cultured human cell-multilayered periosteal sheets. Micron48: 1-10

[28] Huang S, Ingber DE (2005) Cell tension, matrix mechanics, and cancer development. Cancer Cell8: 175-176

[29] Huang J, Chen J, Chesla SE, Yago T, Mehta P, McEver RP, Zhu C, Long M (2004) Quantifying the effects of molecular orientation and length on two-dimensional receptor-ligand binding kinetics. J Biol Chem279: 44915-44923

[30] Huang C, Holfeld J, Schaden W, Orgill D, Ogawa R (2013) Mechanotherapy: revisiting physical therapy and recruiting mechanobiology for a new era in medicine. Trends Mol Med19: 555-564

[31] Ingber DE (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol59: 575-599

[32] Janmey PA, McCulloch CA (2007) Cell mechanics: integrating cell responses to mechanical stimuli. Annu Rev Biomed Eng9: 1-34

[33] Jiang YK, Liu HW, Li H, Wang FJ, Cheng K, Zhou GD, Zhang WJ, Ye ML, Cao YL, Liu W (2011) A proteomic analysis of engineered tendon formation under dynamic mechanical loading in vitro. Biomaterials32: 4085-4095

[34] Kaarniranta K, Elo MA, Sironen RK, Karjalainen HM, Helminen HJ, Lammi MJ (2003) Stress responses of mammalian cells to high hydrostatic pressure. Biorheology40: 87-92

[35] Kang YY, Lu SQ, Ren P, Huo B, Long M (2012) Molecular dynamics simulation of shear- and stretch-induced dissociation of P-selectin/ PSGL-1 complex. Biophys J102: 112-120

[36] Karjalainen HM, Sironen RK, Elo MA, Kaarniranta K, Takigawa M, Helminen HJ, Lammi MJ (2003) Gene expression profiles in chondrosarcoma cells subjected to cyclic stretching and hydrostatic pressure. A cDNA array study. Biorheology40: 93-100

[37] Katsumi A, Milanini J, Kiosses WB, del Pozo MA, Kaunas R, Chien S, Hahn KM, Schwartz MA (2002) Effects of cell tension on the small GTPase Rac. J Cell Biol158: 153-164

[38] Katsumi A, Orr AW, Tzima E, Schwartz MA (2004) Integrins in mechanotransduction. J Biol Chem279: 12001-12004

[39] Kimbrough JM, Salinas-Mondragon R, Boss WF, Brown CS, Sederoff HW (2004) The fast and transient transcriptional network of gravity and mechanical stimulation in the Arabidopsis root apex. Plant Physiol136: 2790-2805

[40] Kurpinski K, Chu J, Wang DJ, Li S (2009) Proteomic profiling of mesenchymal stem cell responses to mechanical strain and TGF-beta 1. Cell Mol Bioeng2: 606-614

[41] Lammi MJ, Inkinen R, Parkkinen JJ, Hakkinen T, Jortikka M, Nelimarkka LO, Jarvelainen HT, Tammi MI (1994) Expression of reduced amounts of structurally altered aggrecan in articularcartilage chondrocytes exposed to high hydrostatic-pressure. Biochem J304: 723-730

[42] Lang M (2007) Lighting up the mechanome. Bridge37: 11-16

[43] Lawrie CH, Gal S, Dunlop HM, Pushkaran B, Liggins AP, Pulford K, Banham AH, Pezzella F, Boultwood J, Wainscoat JS (2008) Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol141: 672-675

[44] Li T (2008) A mechanics model of microtubule buckling in living cells. J Biomech41: 1722-1729

[45] Li YSJ, Haga JH, Chien S (2005) Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech38: 1949-1971

[46] Li H, Chen JA, Zhang Y, Sun SJ, Tao ZL, Long M (2010) Effects of oriented substrates on cell morphology, the cell cycle, and the cytoskeleton in Ros 17/2.8 cells. Sci Chin Life Sci53: 1085-1091

[47] Li JL, Zhang F, Chen JY (2011) An integrated proteomics analysis of bone tissues in response to mechanical stimulation. BMC Syst Biol5: S7

[48] Li J, Rose E, Frances D, Sun Y, You LD (2012) Effect of oscillating fluid flow stimulation on osteocyte mRNA expression. J Biomech45: 247-251

[49] Li M, Li X, Meikle MC, Islam I, Cao T (2013a) Short periods of cyclic mechanical strain enhance triple-supplement directed osteogenesis and bone nodule formation by human embryonic stem cells in vitro. Tissue Eng Part A19: 2130-2137

[50] Li N, Mao D, Lu S, Tong C, Zhang Y, Long M (2013b) Distinct binding affinities of Mac-1 and LFA-1 in neutrophil activation. J Immunol190: 4371-4381

[51] Li Z, Gong YW, Sun SJ, Du Y, Lu DY, Liu XF, Long M (2013c) Differential regulation of stiffness, topography, and dimension of substrates in rat mesenchymal stem cells. Biomaterials34: 7616-7625

[52] Liang S, Fu C, Wagner D, Guo H, Zhan D, Dong C, Long M (2008) Two-dimensional kinetics of beta(2)-integrin and ICAM-1 bindings between neutrophils and melanoma cells in a shear flow. Am J Physiol294: C1604-C1605

[53] Liu MY, Xu J, Tanswell AK, Post M (1994) Inhibition of mechanical strain-induced fetal-rat lung-cell proliferation by gadolinium, a stretch-activated channel blocker. J Cell Physiol161: 501-507

[54] Long M, Sato M, Lim CT, Wu JH, Adachi T, Inoue Y (2011) Advances in experiments and modeling in micro- and nano-biomechanics: a mini review. Cell Mol Bioeng4: 327-339

[55] Lü SQ, Ye ZY, Zhu C, Long M (2006) Quantifying the effects of contact duration, loading rate, and approach velocity on P-selectin-PSGL-1 interactions using AFM. Polymer47: 2539-2547

[56] Lü DY, Liu XF, Gao YX, Huo B, Kang YY, Chen J, Sun SJ, Chen L, Luo XD, Long M (2013) Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model. PLoS ONE8: e74563

[57] Lynch ME, Brooks D, Mohanan S, Lee MJ, Polamraju P, Dent K, Bonassar LJ, van der Meulen MCH, Fischbach C (2013) In vivo tibial compression decreases osteolysis and tumor formation in a human metastatic breast cancer model. J Bone Miner Res28: 2357-2367

[58] MacQueen L, Chebotarev O, Simmons CA, Sun Y (2012) Miniaturized platform with on-chip strain sensors for compression testing of arrayed materials. Lab Chip12: 4178-4184

[59] Malone AMD, Batra NN, Shivaram G, Kwon RY, You LD, Kim CH, Rodriguez J, Jair K, Jacobs CR (2007) The role of actin cytoskeleton in oscillatory fluid flow-induced signaling in MC3T3-E1 osteoblasts. Am J Physiol292: C1830-C1836

[60] Mangala LS, Zhang Y, He Z, Emami K, Ramesh GT, Story M, Rohde LH, Wu H (2011) Effects of simulated microgravity on expression profile of microRNA in human lymphoblastoid cells. J Biol Chem286: 32483-32490

[61] Martinac B (2004) Mechanosensitive ion channels: molecules of mechanotransduction. J Cell Sci117: 2449-2460

[62] McNamara LE, Burchmore R, Riehle MO, Herzyk P, Biggs MJ, Wilkinson CD, Curtis AS, Dalby MJ (2012) The role of microtopography in cellular mechanotransduction. Biomaterials33: 2835-2847

[63] Moraes C, Likhitpanichkul M, Lam CJ, Beca BM, Sun Y, Simmons CA (2013) Microdevice array-based identification of distinct mechanobiological response profiles in layer-specific valve interstitial cells. Integr Biol5: 673-680

[64] Moseyko N, Zhu T, Chang HS, Wang X, Feldman LJ (2002) Transcription profiling of the early gravitropic response in Arabidopsis using high-density oligonucleotide probe microarrays. Plant Physiol130: 720-728

[65] Murrell M, Pontani LL, Guevorkian K, Cuvelier D, Nassoy P, Sykes C (2011) Spreading dynamics of biomimetic actin cortices. Biophys J00: 1400-1409

[66] Nichols HL, Zhang N, Wen XJ (2006) Proteomics and genomics of microgravity. Physiol Genomics26: 163-171

[67] Piltti J, Hayrinen J, Karjalainen HM, Lammi MJ (2008) Proteomics of chondrocytes with special reference to phosphorylation changes of proteins in stretched human chondrosarcoma cells. Biorheology45: 323-335

[68] Plomion C, Pionneau C, Bailleres H (2003) Analysis of protein expression along the normal to tension wood gradient in Eucalyptus gunnii. Holzforschung57: 353-358

[69] Porat Z, Yaron I, Katz BZ, Kam Z, Geiger B (2011) Shear flowinduced formation of tubular cell protrusions in multiple myeloma cells. J Cell Physiol226: 3197-3207

[70] Pozo L, Sanchez-Carrillo JJ, Martinez A, Blanes A, Diaz-Cano SJ (2007) Differential kinetic features by tumour topography in cutaneous small-cell neuroendocrine (Merkel cell) carcinomas. J Eur Acad Dermatol21: 1220-1228

[71] Priam S, Bougault C, Houard X, Gosset M, Salvat C, Berenbaum F, Jacques C (2013) Identification of soluble 14-3-3epsilon as a new subchondral bone mediator involved in cartilage degradation in osteoarthritis. Arthritis Rheumatol65: 1831-1842

[72] Qi YX, Jiang J, Jiang XH, Wang XD, Ji SY, Han Y, Long DK, Shen BR, Yan ZQ, Chien S (2011) PDGF-BB and TGF-beta 1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress. Proc Natl Acad Sci USA108: 1908-1913

[73] Richard MN, Deniset JF, Kneesh AL, Blackwood D, Pierce GN (2007) Mechanical stretching stimulates smooth muscle cell growth, nuclear protein import, and nuclear pore expression through mitogen-activated protein kinase activation. J Biol Chem282: 23081-23088

[74] Rogers RS, Dharsee M, Ackloo S, Sivak JM, Flanagan JG (2012) Proteomics analyses of human optic nerve head astrocytes following biomechanical strain. Mol Cell Proteomics11 (M111): 012302

[75] Schatti O, Grad S, Goldhahn J, Salzmann G, Li Z, Alini M, Stoddart MJ (2011) A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells. Eur Cells Mater22: 214-225

[76] Sem DS, Yu L, Coutts SM, Jack R (2001) Object-oriented approach to drug design enabled by NMR SOLVE: first real-time structural tool for characterizing protein-ligand interactions. J Cell Biochem84: 99-105

[77] Shi Y, Li HW, Zhang XL, Fu YJ, Huang Y, Lui PPY, Tang TT, Dai KR (2011) Continuous cyclic mechanical tension inhibited Runx2 expression in mesenchymal stem cells through RhoA-ERK1/2 pathway. J Cell Physiol226: 2159-2169

[78] Shieh AC, Rozansky HA, Hinz B, Swartz MA (2011) Tumor cell invasion is promoted by interstitial flow-induced matrix priming by stromal fibroblasts. Cancer Res71: 790-800

[79] Silkworth JB, Stehbens WE (1975) Shape of endothelial cells in en face preparations of rabbit blood-vessels. Angiology26: 474-487

[80] Sironen R, Elo M, Kaarniranta K, Helminen HJ, Lammi MJ (2000) Transcriptional activation in chondrocytes submitted to hydrostatic pressure. Biorheology37: 85-93

[81] Sironen RK, Karjalainen HM, Torronen K, Elo MA, Kaarniranta K, Takigawa M, Helminen HJ, Lammi MJ (2002) High pressure effects on cellular expression profile and mRNA stability. A cDNA array analysis. Biorheology39: 111-117

[82] Soltz MA, Ateshian GA (2000) Interstitial fluid pressurization during confined compression cyclical loading of articular cartilage. Ann Biomed Eng28: 150-159

[83] Song MJ, Brady-Kalnay SM, McBride SH, Phillips-Mason P, Dean D, Tate MLK (2012) Mapping the mechanome of live stem cells using a novel method to measure local strain fields in situ at the fluid-cell interface. PLoS ONE7: e43601

[84] Song MJ, Dean D, Knothe Tate ML (2013) Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds. Biomaterials34 : 5766-5775

[85] Stamenovic D, Ingber DE (2002) Models of cytoskeletal mechanics of adherent cells. Biomech Model Mechanobiol1: 95-108

[86] Sterky F, Bhalerao RR, Unneberg P, Segerman B, Nilsson P, Brunner AM, Charbonnel-Campaa L, Lindvall JJ, Tandre K, Strauss SH (2004) A populus EST resource for plant functional genomics. Proc Natl Acad Sci USA101: 13951-13956

[87] Steward RL, Cheng CM, Ye JD, Bellin RM, LeDuc PR (2011) Mechanical stretch and shear flow induced reorganization and recruitment of fibronectin in fibroblasts. Sci Rep1: 147

[88] Sun SJ, Gao YX, Shu NJ, Tang ZM, Tao ZL, Long M (2008) A novel counter sheet-flow sandwich cell culture device for mammalian cell growth in space. Microgravity Sci Technol20: 115-120

[89] Sun GY, Zhang Y, Huo B, Long M (2009) Parametric analysis for monitoring 2D kinetics of receptor-ligand binding. Cell Mol Bioeng2: 495-503

[90] Swaminathan V, Mythreye K, O’Brien ET, Berchuck A, Blobe GC, Superfine R (2011) Mechanical stiffness grades metastatic potential in patient tumor cells and in cancer cell lines. Cancer Res71: 5075-5080

[91] Tamura I, Rosenbloom J, Macarak E, Chaqour B (2001) Regulation of Cyr61 gene expression by mechanical stretch through multiple signaling pathways. Am J Physiol281: C1524-C1532

[92] Tan SD, de Vries TJ, Kuijpers-Jagtman AM, Semeins CM, Elverts V, Klein-Nulend J (2007) Osteocytes subjected to fluid flow inhibit osteoclast formation and bone resorption. Bone41: 745-751

[93] Tse JM, Cheng G, Tyrrell JA, Wilcox-Adelman SA, Boucher Y, Jain RK, Munn LL (2012) Mechanical compression drives cancer cells toward invasive phenotype. Proc Natl Acad Sci USA109: 911-916

[94] van Loon JJWA (2009) Mechanomics and physicomics in gravisensing. Microgravity Sci Technol21: 159-167

[95] Wang JHC (2006) Mechanobiology of tendon. J Biomech39: 1563-1582

[96] Wang YX, Shyy JYJ, Chien S (2008) Fluorescence proteins, live-cell imaging, and mechanobiology: seeing is believing. Annu Rev Biomed Eng10: 1-38

[97] Wang XL, Fu A, Spiro C, Lee HC (2009) Proteomic analysis of vascular endothelial cells-effects of laminar shear stress and high glucose. J Proteomics Bioinform2: 445-454

[98] Ward DF, Salasznyk RM, Klees RF, Backiel J, Agius P, Bennett K, Boskey A, Plopper GE (2007) Mechanical strain enhances extracellular matrix-induced gene focusing and promotes osteogenic differentiation of human mesenchymal stem cells through an extracellular-related kinase-dependent pathway. Stem Cells Dev16: 467-479

[99] Wirtz D, Konstantopoulos K, Searson PC (2011) The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer11: 512-522

[100] Wright MO, Nishida K, Bavington C, Godolphin JL, Dunne E, Walmsley S, Jobanputra P, Nuki G, Salter DM (1997) Hyperpolarisation of cultured human chondrocytes following cyclical pressure-induced strain: evidence of a role for alpha 5 beta 1 integrin as a chondrocyte mechanoreceptor. J Orthop Res15: 742-747

[101] Xu J, Khor KA, Sui J, Zhang J, Tan TL, Chen WN (2008) Comparative proteomics profile of osteoblasts cultured on dissimilar hydroxyapatite biomaterials: an iTRAQ-coupled 2-D LC-MS/MS analysis. Proteomics8: 4249-4258

[102] Yang R, Amir J, Liu HB, Chaqour B (2008) Mechanical strain activates a program of genes functionally involved in paracrine signaling of angiogenesis. Physiol Genomics36: 1-14

[103] Yang F, Gao YX, Zhang Y, Chen J, Long M (2009) Developing a microfluidic-based system to quantify cell capture efficiency. Sci China Ser C52 : 173-181

[104] Yi W, Sun Y, Wei XF, Gu CH, Dong XC, Kang XJ, Guo SZ, Dou KF (2010) Proteomic profiling of human bone marrow mesenchymal stem cells under shear stress. Mol Cell Biochem341: 9-16

[105] You LD, Cowin SC, Schaffler MB, Weinbaum S (2001) A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix. J Biomech34: 1375-1386

[106] Zayzafoon M, Meyers VE, McDonald JM (2005) Microgravity: the immune response and bone. Immunol Rev08: 267-280

[107] Zdero R, McConnell AJ, Peskun C, Syed KA, Schemitsch EH (2011) Biomechanical measurements of torsion-tension coupling in human cadaveric femurs. J Biomech Eng33: 014501-1-014501-6

[108] Zhan DY, Zhang Y, Long M (2012) Spreading of human neutrophils on an ICAM-1-immobilized substrate under shear flow. Chin Sci Bull7: 769-775

[109] Zhang Y, Sun GY, Lu SQ, Li N, Long M (2008) Low spring constant regulates P-selectin-PSGL-1 bond rupture. Biophys J95: 5439-5448

[110] Zhou D, Lee HS, Villarreal F, Teng A, Lu E, Reynolds S, Qin C, Smith J, Sung KLP (2005) Differential MMP-2 activity of ligament cells under mechanical stretch injury: an in vitro study on human ACL and MCL fibroblasts. J Orthop Res23: 949-957

RIGHTS & PERMISSIONS

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.