Editorial Cite This: ACS Biomater. Sci. Eng. 2019, 5, 3685−3687
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Special Issue: Biomaterials for Cell Mechanobiology culture conditions that integrated substrate stiffness, cell geometry, and cell−cell contacts step by step. Their work suggests a “superimposed effect” of supplying mechanobiological stimuli to promote cell behaviors. Although 2D investigations of cell mechanobiology can provide important insights into cell responses to biophysical cues, they are not able to recapitulate the in vivo 3D tissue microenvironment. Chen and Zhao6 therefore reviewed current techniques for biofabrication of 3D microtissues and summarized the geometrically guided formation of various microtissues and their biological characteristics. Among these techniques, Bose and colleagues7 exploited a 3D system to study the effects of geometrical constraints on microtissues and suggested an interplay among geometrical constraints, alignment, density, and mechanics of the 3D ECM tissue construct. To overcome the laborious fabrication process in soft-lithography, Du et al.8 developed a 3D bioprinting method for fabricating GelMA hydrogel patterns with a coated thermoresponsive surface and successfully controlled collective cell migration and myotube formation. Cell−ECM interactions within a physiological niche comprises various topographical cues that can be sensed by cells and, consequently, direct cells to promote distinct behaviors, such as proliferation, migration, and differentiation. Noh et al.9 fabricated magnetic nanoparticle-embedded hydrogel sheet with a groove pattern to control endothelial progenitor cell behaviors, including proliferation, alignment, and elongation for wound healing application. Pramotton et al.10 took advantage of both topology and topographymediated response of epithelial cells and achieved an optimized expansion of epithelial cells. In addition to modulating cell proliferation and migration using topography-engineered biomaterials, Yang et al.’s work11 demonstrated that neuronal differentiation can be induced by neural stem cells in response to a stress-responsive PMDS nanowrinkle topography. Further, they found that differentiation is time-dependent, discovering a “time-retention effect” of topography cues on NSC differentiation fate. In line with Kim’s findings, Kwong et al.12 discovered that mouse myoblasts can “memorize” the previous experience of culture conditions and displayed different chiral behaviors on micropatterned substrates. At the cell−ECM interface, cells form adhesive links such as focal adhesions (FAs) to sense and interact with ECM structures. FA-based ECM interactions are important in mediating cell contractility, and thus influences various cell properties and functions like stem cell differentiation. Xia et al.13 explored the molecular composition and nanostructural organization of FAs in mouse embryonic stem cells mESCs. Jo et al.14 further developed an image analysis method for quantifying integrin-mediated molecular tension at the cell− ECM interface by using a quenched tension gauge tether
Over the past two decades, it has become increasingly clear that cell behaviors are not only regulated by soluble biochemical factors but also by biophysical cues in the cellular/tissue microenvironment. Thus, cell mechanobiology has emerged as a highly interdisciplinary research field investigating the mechanosensing and mechanotransduction processes, from as early as embryogenesis to cancer development and aging. The development of cell mechanobiology research highlights the great significance of applying functional biomaterials for revealing the key mechanobiological machineries that direct cell/tissue fate and function in health and disease. Biomaterials mimicking human physiological and pathological conditions with ideal biocompatibility, tunable mechanical properties, and controllable architectures have thrived rapidly for revealing adaptive and integrated cellular behaviors through cell−extracellular matrix (ECM) interactions. Engineering biomaterials also contribute to the success of clinical treatment for diseases and develop therapies through intervening the interactions between cells and cell microenvironment. This timely special issue on Biomaterials for Cell Mechanobiology highlights some of the most recent research in the field of cell mechanobiology in the context of biomaterials, tissue engineering, and computational modeling. A combination of review and original research articles are presented in this issue to provide a broad survey of the current work in this field. Both experimental and theoretical works found in this issue can elucidate a better understanding of cell mechanobiology. In the endeavor to study cell mechanobiology, biomaterials engineered with tunable mechanical properties and delicate micro/nanoscale architectures have become powerful tools to emulate ECM biophysical cues and interrogate their regulatory roles in biochemical signaling and cell/tissue functions via diverse mechanobiological machineries. One of the most widely employed biomaterials for cell mechanobiology studies is hyaluronic acid (HA). HA, an ECM component that comprises diverse tissues, is highly compatible with chemical modifications, rendering it an excellent biomimetic material to control the mechanical properties of ECM tissue constructs and probe cell mechanosensing and mechanotransduction. Wolf et al.1 reviewed how HA-based signaling regulates cell functions and applying these findings to create cell-instructive biomaterials. Using HA-based biomaterials, Davidson et al.2 developed a fibrous network with controllable stiffness to explore the mechanical influence of ECM fibers on myofibroblast differentiation. Besides modulating stiffness, Jamilpour et al.3 revealed that cardiomyocytes can collectively adapt to geometrical confinements and successfully achieved multicellular clusters. Similarly, Zhu et al.4 discovered that matrix rigidity and geometric curvature can modulate the spontaneous fusion and stability of multinucleated giant cells, which are thought to contribute to tumor development and drug resistance. Furthermore, Rodriguez et al.5 successfully produced more structurally and functionally mature human embryonic stem cell-derived cardiomyocytes by optimizing © 2019 American Chemical Society
Special Issue: Biomaterials for Mechanobiology Received: July 25, 2019 Published: August 12, 2019 3685
DOI: 10.1021/acsbiomaterials.9b01123 ACS Biomater. Sci. Eng. 2019, 5, 3685−3687
ACS Biomaterials Science & Engineering
Editorial
differentiation have been outlined. Intrinsically, cell mechanobiological processes are complex and involve a coordination of multiple cell−ECM interactive signals that trigger different mechanosensitive pathways. However, with advances in biomaterials engineering and modeling, a more thorough and in-depth understanding of cell mechanobiology will be achieved, enabling the transition of next-generation cell studies and disease interventions.
(qTGT) system. This tool may be useful to study cell tension during migration which requires longitudinal live-cell measurements. Using traction force microscopy, Dean et al.15 discovered that decreasing intercellular tension can enhance the formation of smooth muscle cell leader cells at the wound edge during collective cell migration. As the cell-generated contractile forces are fundamental in controlling cell−ECM interactions and cell cytoskeleton (CSK) organization and activating multiple biochemical signal cascades, Matellan et al.16 summarized current techniques for quantifying cell contractile force and biomechanical properties. They further provided a review on how to apply mechanical force on cells to study the diversity of mechanosensing and mechanotransduction processes. Particularly, Lee and colleagues17 reviewed current techniques for profiling and quantifying cancer cellECM interactions and provided a thorough summary of the mechanical properties and dynamics that comprise cancer cell mechanosensing and progression. Focusing on the collective cell migration behaviors in cancer progression, Spatarelu et al.18 summarized a recent development of both experimental and computational methods and hypotheses regarding the biomechanics of cancer cell collective migration. By combining confined microchannels with elasticity-modulated microbeads, Ren et al.19 developed a microfluidic platform for distinguishing non-neoplastic and cancer cell elasticities, demonstrating its potential application for cancer cell mechanophenotyping. In the process of mechanosensing and mechanotransduction, the cell CSK plays fundamental roles in maintaining cell integrity, generating contractile forces, and transmitting biomechanical signals. Fan et al.20 reviewed the mechanical roles of a single important component of CSK architecturefactinin regulating stem cell differentiation. Multiple intra/ extracellular proteins associated with F-actin and its functions in regulating stem cell differentiation have also been discussed, providing a thorough understanding of biophysical determinants of stem cell fate decisions. When probing the functional link between the actin-based molecular networks and cell biomechanical properties in response to mechanical cues, theoretical modeling and simulation studies provide critical insights. Gong et al.21 provided a review on current approaches for modeling and simulations to understand the relationship between CSK dynamics and observed cell mechanical properties and behaviors. Hassan et al.22 developed a mechanical model and successfully deciphered the behavioral mechanisms of cell durotaxis from discrete interactions between cells and the mechanical properties underlying ECM, such as elasticity, viscosity, and stiffness. Using porcine brain and brain-mimetic hydrogels as models, Calhoun et al.23 found that the inclusion of viscosity effects in mechanical modeling can better recapitulate the mechanical characteristics of these biological tissues and ECM-based hydrogels, which may deepen our understanding of the cellular response to biomaterials. In summary, this special issue highlights the most recent achievements of exploring cell mechanobiology from engineering novel biomaterials to developing theoretical models. Advances in tissue-engineered constructs, molecular tools, and computational methods can permit studies to precisely measure and probe cell responses to diverse ECM mechanical cues. At the same time, an elaborate summary of current approaches, theories, and hypotheses that underlie the biophysical regulation of cell behaviors, including cell proliferation, migration, cancer development, and stem cell
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Weiqiang Chen, Guest Editor Deok-Ho Kim, Guest Editor Chwee Teck Lim, Guest Editor AUTHOR INFORMATION
Notes
Views expressed in this editorial are those of the authors and not necessarily the views of the ACS.
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REFERENCES
(1) Wolf, K. J.; Kumar, S. Hyaluronic Acid: Incorporating the Bio into the Material. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/ acsbiomaterials.8b01268. (2) Davidson, M. D.; Song, K. H.; Lee, M.-H.; Llewellyn, J.; Du, Y.; Baker, B. M.; Wells, R. G.; Burdick, J. A. Engineered Fibrous Networks To Investigate the Influence of Fiber Mechanics on Myofibroblast Differentiation. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01276. (3) Jamilpour, N.; Nam, K.-H.; Gregorio, C. C.; Wong, P. K. Probing Collective Mechanoadaptation in Cardiomyocyte Development by Plasma Lithography Patterned Elastomeric Substrates. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b00815. (4) Zhu, P.; Tseng, N.-H.; Xie, T.; Li, N.; Fitts-Sprague, I.; Peyton, S. R.; Sun, Y. Biomechanical microenvironment regulates fusogenicity of breast cancer cells. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/ acsbiomaterials.8b00861. (5) Rodriguez, M. L.; Beussman, K. M.; Chun, K. S.; Walzer, M. S.; Yang, X.; Murry, C. E.; Sniadecki, N. J. Substrate Stiffness, Cell Anisotropy, and Cell−Cell Contact Contribute to Enhanced Structural and Calcium Handling Properties of Human Embryonic Stem Cell-Derived Cardiomyocytes. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01256. (6) Chen, Z.; Zhao, R. Engineered tissue development in biofabricated 3D geometrical confinement−a review. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01195. (7) Bose, P.; Eyckmans, J.; Nguyen, T. D.; Chen, C. S.; Reich, D. H. Effects of Geometry on the Mechanics and Alignment of ThreeDimensional Engineered Microtissues. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01183. (8) Du, W.; Hong, S.; Scapin, G.; Goulard, M.; Shah, D. I. Directed Collective Cell Migration Using Three-Dimensional Bioprinted Micropatterns on Thermoresponsive Surfaces for Myotube Formation. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01359. (9) Noh, M.; Choi, Y. H.; An, Y.-H.; Tahk, D.; Cho, S.; Yoon, J. W.; Jeon, N. L.; Park, T. H.; Kim, J.; Hwang, N. S. Magnetic nanoparticleembedded hydrogel sheet with a groove pattern for wound healing application. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01307. (10) Pramotton, F. M.; Robotti, F.; Giampietro, C.; Lendenmann, T.; Poulikakos, D.; Ferrari, A. Optimized topological and topographical expansion of epithelia. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01346. (11) Yang, S. S.; Cha, J.; Cho, S.-W.; Kim, P. Time-dependent retention of nanotopographical cues in differentiated neural stem cells. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01057. (12) Kwong, H. K.; Huang, Y.; Bao, Y.; Lam, M. L.; Chen, T.-H. Remnant Effects of Culture Density on Cell Chirality After Reseeding. 3686
DOI: 10.1021/acsbiomaterials.9b01123 ACS Biomater. Sci. Eng. 2019, 5, 3685−3687
ACS Biomaterials Science & Engineering
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ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01364. (13) Xia, S.; Yim, E. K.; Kanchanawong, P. Molecular organization of integrin-based adhesion complexes in mouse Embryonic Stem Cells. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01124. (14) Jo, M. H.; Cottle, W. T.; Ha, T. Real-time measurement of molecular tension during cell adhesion and migration using multiplexed differential analysis of tension gauge tethers. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01216. (15) Dean, Z. S.; Jamilpour, N.; Slepian, M. J.; Wong, P. K. Decreasing Wound Edge Stress Enhances Leader Cell Formation during Collective Smooth Muscle Cell Migration. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01222. (16) Matellan, C.; del Ri′o Herna′ndez, A. E. Where no hand has gone before: probing mechanobiology at the cellular level. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01206. (17) Lee, G.; Han, S.-B.; Lee, J.-H.; Kim, H.-W.; Kim, D.-H. Cancer Mechanobiology: Microenvironmental Sensing and Metastasis. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01230. (18) Spatarelu, C.-P.; Zhang, H.; Nguyen, D. T.; Han, X.; Liu, R.; Guo, Q.; Notbohm, J.; Fan, J.; Liu, L.; Chen, Z. Biomechanics of Collective Cell Migration in Cancer Progression: Experimental and Computational Methods. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01428. (19) Ren, J.; Li, J.; Li, Y.; Xiao, P.; Liu, Y.; Tsang, C. M.; Tsao, S.W.; Lau, D.; Chan, K. W.; Lam, R. H. Elasticity-modulated microbeads for classification of floating normal and cancer cells using confining microchannels. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01273. (20) Fan, Y.-L.; Zhao, H.-C.; Li, B.; Zhao, Z.-L.; Feng, X.-Q. Mechanical roles of F-actin in the differentiation of stem cells: A review. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.9b00126. (21) Gong, B.; Wei, X.; Qian, J.; Lin, Y. Modeling and simulations of the dynamic behaviors of actin-based cytoskeletal networks. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01228. (22) Hassan, A.-R.; Biel, T.; Kim, T. Mechanical Model for Durotactic Cell Migration. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01365. (23) Calhoun, M.; Bentil, S. A.; Elliott, E.; Otero, J. J.; Winter, J. O.; Dupaix, R. B. Beyond Linear Elastic Modulus: Viscoelastic Models for Brain and Brain Mimetic Hydrogels. ACS Biomater. Sci. Eng. 2019, DOI: 10.1021/acsbiomaterials.8b01390.
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DOI: 10.1021/acsbiomaterials.9b01123 ACS Biomater. Sci. Eng. 2019, 5, 3685−3687
