J. Semicond. > 2020, Volume 41 > Issue 4 > 041607, doi: 10.1088/1674-4926/41/4/041607
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REVIEWS

Designer substrates and devices for mechanobiology study

Wang Xi, Delphine Delacour and Benoit Ladoux

+ Author Affiliations

 Corresponding author: Wang Xi, Wang.XI@ijm.fr; Benoit Ladoux, benoit.ladoux@ijm.fr

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Abstract: Both biological and engineering approaches have contributed significantly to the recent advance in the field of mechanobiology. Collaborating with biologists, bio-engineers and materials scientists have employed the techniques stemming from the conventional semiconductor industry to rebuild cellular milieus that mimic critical aspects of in vivo conditions and elicit cell/tissue responses in vitro. Such reductionist approaches have help to unveil important mechanosensing mechanism in both cellular and tissue level, including stem cell differentiation and proliferation, tissue expansion, wound healing, and cancer metastasis. In this mini-review, we discuss various microfabrication methods that have been applied to generate specific properties and functions of designer substrates/devices, which disclose cell-microenvironment interactions and the underlying biological mechanisms. In brief, we emphasize on the studies of cell/tissue mechanical responses to substrate adhesiveness, stiffness, topography, and shear flow. Moreover, we comment on the new concepts of measurement and paradigms for investigations of biological mechanotransductions that are yet to emerge due to on-going interdisciplinary efforts in the fields of mechanobiology and microengineering.

Key words: designer substrates and devices, microfabrication, mechanobiology, microengineering, tissue mechanics, microfluidics



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Fig. 1.  (Color online) Microengineered synthetic substrates for cell/tissue mechanics studies. The properties of a substratum can be modified to adjust the cell/material interactions, such as surface topographies, stiffness, and adhesiveness. In addition, mechanical probes can be integrated into the substrate to detect the force in tissue. These include microbeads in the traction force microscopy and elastomeric micro-pillars.

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Fig. 2.  (Color online) Molecular dynamics at adhesion complexes. The actin network as a mechanosensitive machine connecting the cell to its substrate and neighbors. The building of a stable focal adhesion (FA) complex for cell–substrate adhesion. Actomyosin forces apply on the FA at a fixed speed and the rate of force increase in the complex increases proportionally with the ECM stiffness. To avoid the destabilization and detachment of the FA, the binding-unbinding dynamics of the transmembrane protein, integrin, that connects the cells to the substrate needs to be equal to the force loading rate in the complex. Another force buffer and mechanosensor in the complex is Talin. Its unfolding at ~ 10 pN at the normal rate of force loading in cells lead to vinculin binding to recruit more actin fibers, thus reinforcing the FA.

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Fig. 3.  (Color online) Methods for patterning adhesive surfaces. Semiconductor-based technologies has allowed the development of micro-contact printing and micro-stenciling for patterning biomolecules with define shapes. Later, researchers developed other techniques for this purpose, including Dip-pen lithography and UV-based patterning.

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Fig. 4.  (Color online) Methods for engineering substrate elasticity and viscosity. Conventionally, by controlling the cross-linking degree in elastomers, one could adjust the viscoelasticity of a gel. Another approach to change substrate rigidity involving photolithography is to pattern pillars of different shapes.

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Fig. 5.  (Color online) Topography cues influences cell adhesion and migration. (a) Scanning electron micrographs (SEMs) showing cells aligned to the nano-lines (Reproduced from Ref. [63]). (b) 3D confinement, such as microtubes, leads to amoeboid-like migration mode in neural stem cells (Reproduced from Ref. [38]).

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Fig. 6.  (Color online) Shear stress influences cell adherens junction (AJ) and filopodia protrusion. (a) At AJs, a higher force transmitted from F-actin caused by other factors (such as shear) leads to α-catenin unfolding and subsequently the recruitment of vinculin to stabilize the AJ structure. (b) SEMs showing filopodia formation in human cancer cells in response to wall shear stress (WSS) (Reproduced from Ref. [80]).

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[1]
Xi W, Saw T B, Delacour D, et al. Material approaches to active tissue mechanics. Nat Rev Mater, 2019, 4(1), 23 doi: 10.1038/s41578-018-0066-z
[2]
Prost J, Jülicher F, Joanny J F. Active gel physics. Nat Phys, 2015, 11(2), 111 doi: 10.1038/nphys3224
[3]
Marchetti M C, Joanny J F, Ramaswamy S, et al. Hydrodynamics of soft active matter. Rev Mod Phys, 2013, 85(3), 1143 doi: 10.1103/RevModPhys.85.1143
[4]
Needleman D, Dogic Z. Active matter at the interface between materials science and cell biology. Nat Rev Mater, 2017, 2, 17048 doi: 10.1038/natrevmats.2017.48
[5]
Grashoff C, Hoffman B D, Brenner M D, et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature, 2010, 466(7303), 263 doi: 10.1038/nature09198
[6]
Giannone G, Dubin-Thaler B J, Döbereiner H G, et al. Periodic lamellipodial contractions correlate with rearward actin waves. Cell, 2004, 116(3), 431 doi: 10.1016/S0092-8674(04)00058-3
[7]
Ray A, Lee O, Win Z, et al. Anisotropic forces from spatially constrained focal adhesions mediate contact guidance directed cell migration. Nat Commun, 2017, 8, 14923 doi: 10.1038/ncomms14923
[8]
Jiang X, Bruzewicz D A, Wong A P, et al. Directing cell migration with asymmetric micropatterns. Proc Natl Acad Sci USA, 2005, 102(4), 975 doi: 10.1073/pnas.0408954102
[9]
Chen B, Kumar G, Co C C, et al. Geometric control of cell migration. Sci Rep, 2013, 3(1), 1 doi: 10.1038/srep02827
[10]
Johnson H E, King S J, Asokan S B, et al. F-actin bundles direct the initiation and orientation of lamellipodia through adhesion-based signaling. J Cell Biol, 2015, 208(4), 443 doi: 10.1083/jcb.201406102
[11]
Engler A J, Sen S, Sweeney H L, et al. Matrix elasticity directs stem cell lineage specification. Cell, 2006, 126(4), 677 doi: 10.1016/j.cell.2006.06.044
[12]
Naganathan S R, Middelkoop T C, Fürthauer S, et al. Actomyosin-driven left-right asymmetry: from molecular torques to chiral self organization. Curr Opin Cell Biol, 2016, 38, 24 doi: 10.1016/j.ceb.2016.01.004
[13]
Tee Y H, Shemesh T, Thiagarajan V, et al. Cellular chirality arising from the self-organization of the actin cytoskeleton. Nat Cell Biol, 2015, 17(4), 445 doi: 10.1038/ncb3137
[14]
Gupta M, Sarangi B R, Deschamps J, et al. Adaptive rheology and ordering of cell cytoskeleton govern matrix rigidity sensing. Nat Commun, 2015, 6(1), 1 doi: 10.1038/ncomms8525
[15]
Trichet L, Le Digabel J, Hawkins R J, et al. Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness. Proc Natl Acad Sci USA, 2012, 109(18), 6933 doi: 10.1073/pnas.1117810109
[16]
Zemel A, Rehfeldt F, Brown A E, et al. Optimal matrix rigidity for stress-fibre polarization in stem cells. Nat Phys, 2010, 6(6), 468 doi: 10.1038/nphys1613
[17]
Levina E M, Domnina L V, Rovensky Y A, et al. Cylindrical substratum induces different patterns of actin microfilament bundles in nontransformed and in ras-transformed epitheliocytes. Exp Cell Res, 1996, 229(1), 159 doi: 10.1006/excr.1996.0354
[18]
Svitkina T M, Rovensky Y A, Bershadsky A D, et al. Transverse pattern of microfilament bundles induced in epitheliocytes by cylindrical substrata. J Cell Sci, 1995, 108(2), 735 doi: 10.1083/jcb.128.4.699
[19]
Sun B, Xie K, Chen T H, et al. Preferred cell alignment along concave microgrooves. RSC Adv, 2017, 7(11), 6788 doi: 10.1039/C6RA26545F
[20]
Biton Y Y, Safran S A. The cellular response to curvature-induced stress. Phys Biol, 2009, 6(4), 046010 doi: 10.1088/1478-3975/6/4/046010
[21]
Bade N D, Kamien R D, Assoian R K, et al. Curvature and Rho activation differentially control the alignment of cells and stress fibers. Sci Adv, 2017, 3(9), e1700150 doi: 10.1126/sciadv.1700150
[22]
De R, Zemel A, Safran S A. Dynamics of cell orientation. Nat Phys, 2007, 3(9), 655 doi: 10.1038/nphys680
[23]
Livne A, Bouchbinder E, Geiger B. Cell reorientation under cyclic stretching. Nat Commun, 2014, 5, 3938 doi: 10.1038/ncomms4938
[24]
Sidhaye V K, Schweitzer K S, Caterina M J, et al. Shear stress regulates aquaporin-5 and airway epithelial barrier function. Proc Natl Acad Sci USA, 2008, 105(9), 3345 doi: 10.1073/pnas.0712287105
[25]
Ladoux B, Mège R M. Mechanobiology of collective cell behaviours. Nat Rev Molecul Cell Biol, 2017, 18(12), 743 doi: 10.1038/nrm.2017.98
[26]
Wong S, Guo W H, Wang Y L. Fibroblasts probe substrate rigidity with filopodia extensions before occupying an area. Proc Natl Acad Sci USA, 2014, 111(48), 17176 doi: 10.1073/pnas.1412285111
[27]
Saez A, Ghibaudo M, Buguin A, et al. Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates. Proc Natl Acad Sci USA, 2007, 104(20), 8281 doi: 10.1073/pnas.0702259104
[28]
Wang X, Li S, Yan C, et al. Fabrication of RGD micro/nanopattern and corresponding study of stem cell differentiation. Nano Lett, 2015, 15(3), 1457 doi: 10.1021/nl5049862
[29]
Saw T B, Doostmohammadi A, Nier V, et al. Topological defects in epithelia govern cell death and extrusion. Nature, 2017, 544(7649), 212 doi: 10.1038/nature21718
[30]
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    Received: 02 March 2020 Revised: 02 April 2020 Online: Accepted Manuscript: 03 April 2020Uncorrected proof: 05 April 2020Published: 10 April 2020

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      Article Navigation >  Journal of Semiconductors  > 2020  >  41(4): 041607
      Wang Xi, Delphine Delacour, Benoit Ladoux. Designer substrates and devices for mechanobiology study[J]. Journal of Semiconductors, 2020, 41(4): 041607. doi: 10.1088/1674-4926/41/4/041607 W Xi, D Delacour, B Ladoux, Designer substrates and devices for mechanobiology study[J]. J. Semicond., 2020, 41(4): 041607. doi: 10.1088/1674-4926/41/4/041607.Export: BibTex EndNote
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      Wang Xi, Delphine Delacour, Benoit Ladoux. Designer substrates and devices for mechanobiology study[J]. Journal of Semiconductors, 2020, 41(4): 041607. doi: 10.1088/1674-4926/41/4/041607

      W Xi, D Delacour, B Ladoux, Designer substrates and devices for mechanobiology study[J]. J. Semicond., 2020, 41(4): 041607. doi: 10.1088/1674-4926/41/4/041607.
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      Designer substrates and devices for mechanobiology study

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      • Cell Adhesion and Mechanics, Institut Jacques Monod, CNRS UMR7592, Paris Diderot University, 75205 Paris Cedex 13, France

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