Tweaking signaling cascade by artificial nano-organelles in cells - NCCR MSE

Tweaking signaling cascade by artificial nano-organelles in cells


Forces matter in molecular systems engineering. Engineered microsystems, when exposed to living tissues, will be strained by mechanical forces, for example when exposed to shear forces, or when colliding with blood vessel walls or grabbed by our immune cells. Since one central goal of this NCCR is to engineer a new generation of engineered micro-or nanosystems that can interfere at the functional level with cells and tissues in vivo, we are particularly interested in asking how their mechanical characteristics have to be designed to best serve their functions. While major efforts in the past went into the chemical design of drug delivery systems, the mechanobiology of cells and tissues, and how this co-regulates uptake and other cell functions, has been mostly ignored in their design. 

To learn from nature how to best engineer molecular factories that survive the strenuous conditions found in living organisms, we currently investigate the methods by which cellular microorganisms interact with biological systems, and quantify the forces involved and how this knowledge can be utilized to engineer synthetic micro and nano-objects. Once microbes enter the body, for example, they often adhere to tissue surfaces or fibers. It is thus not sufficient that macrophages and other immune cells recognize just the biochemical signature of molecular factories. Either one can design these molecular factories to be “invisible” to the immune system.

Alternatively, if the goal is to have these factories enter cells, it is important that cells can apply sufficient forces to rupture the adhesive contacts by which these objects hold on to tissue surfaces, and that the cells can subsequently form a phagocytotic cup around the objects which then allows their phagocytosis. One central goal of us is thus to develop assays that allow us to test for mechanical processes by which cells of different organs as well as circulating cells interact with microbes and how this can best mimicked by engineered biomimetic objects.

An associated goal is to develop cellular read out systems to learn how these mechanical processes affect cell signaling responses. Since we anticipate a broad range of medical applications made possible by the engineered microsystems of this NCCR, our goals include to ask how we need to learn (1) how sessile cells (e.g. fibroblasts) and circulating immune cells (e.g. macrophages) recognize and interact with the surface chemistry, shape and physical properties of the microsystems, and (2) how to (re)engineer such containers either to promote, for example, the uptake by cells for longterm applications in immune therapy, or to reduce the uptake by cells for other applications. This includes investigating how size and shape affect uptake by macrophages and to analyze spatial-temporal evolution of the forces involved, and how the mechanical forces cells apply to such engineered objects impede or steer cellular signaling.

Read more: 

  • ETH News about "Montagelinie im Nano-Format" (26.8.2014).
  • Interview with Viola Vogel in the newsletter MOLEKULAR-ia (issue October 2015, Vol. 1).  


J. L. Mehl, A. Earle, J. Lammerding, M. Mhlanga, V. Vogel, N. Jain “Blockage of lamin-A/C loss diminishes the pro-inflammatory macrophage response“ iScience 2022. [DOI]
N. Jain, T. Shahal, T. Gabrieli, N. Gilat, D. Torchinsky, Y. Michaeli, V. Vogel, Y. Ebenstein “Global modulation in DNA epigenetics during pro-inflammatory macrophage activation“ Epigenetics 2019, 14:1183-1193. [DOI]
N. Jain, J. Moeller, V. Vogel “Mechanobiology of Macrophages: How Physical Factors Coregulate Macrophage Plasticity and Phagocytosis“ Annu. Rev. Biomed. Eng. 2019, 21(1):267-97. [DOI]
N. Jain, V. Vogel “Spatial confinement downsizes the inflammatory response of macrophages“ Nat. Mater. 2018. [DOI]
J. Shiu, L. Aires, Z. Lin, V. Vogel “Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction“ Nat. Cell Biol. 2018. [DOI]
S. Arnoldini, A. Moscaroli, M. Chabria, M. Hilbert, S. Hertig, R. Schibli, M. Béhé, V. Vogel “Novel peptide probes to assess the tensional state of fibronectin fibers in cancer“ Nat. Commun. 2017. [DOI]
S. Schuerle, I. A. Vizcarra, J. Moeller, M. S. Sakar, B. Özkale, A. M. Lindo, F. Mushtaq, I. Schoen, S. Pané, V. Vogel, B. J. Nelson “Robotically controlled microprey to resolve initial attack modes preceding phagocytosis“ Sci. Rob. 2017, 2:eaah6094. [DOI]
J. Foolen, J. Shiu, M. Mitsi, Y. Zhang, C. S. Chen, V. Vogel “Full-Length Fibronectin Drives Fibroblast Accumulation at the Surface of Collagen Microtissues during Cell-Induced Tissue Morphogenesis“ PLoS One 2016, 11:e0160369. [DOI]
M. A. Burkhardt, J. Waser, V. Milleret, I. Gerber, M. Y. Emmert, J. Foolen, S. P. Hoerstrup, F. Schlottig, V. Vogel “Synergistic interactions of blood-borne immune cells, fibroblasts and extracellular matrix drive repair in an in vitro peri-implant wound healing model“ Sci. Rep. 2016, 6:21071. [DOI]
I. Avalos Vizcarra, V. Hosseini, P. Kollmannsberger, S. Meier, S. S. Weber, M. Arnoldini, M. Ackermann, V. Vogel “How type 1 fimbriae help Escherichia coli to evade extracellular antibiotics“ Sci. Rep. 2016, 6:DOI: 10.1038/srep18109. [DOI]
T. O. Ihalainen, L. Aires, F. A. Herzog, R. Schwartlander, J. Moeller, V. Vogel “Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension“ Nat. Mater. 2015, 14:1252. [DOI]
K. E. Kubow, R. Vukmirovic, L. Zhe, E. Klotzsch, M. L. Smith, D. Gourdon, S. Luna, V. Vogel “Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix“ Nat. Commun. 2015, 6:8026. [DOI]
S. M. Früh, I. Schoen, J. Ries, V. Vogel “Molecular architecture of native fibronectin fibrils“ Nat. Commun. 2015, 6:7275. [DOI]
D. Steuerwald, S. M. Fruh, R. Griss, R. D. Lovchik, V. Vogel “Nanoshuttles propelled by motor proteins sequentially assemble molecular cargo in a microfluidic device“ Lab Chip 2014, 14:3729-38. [DOI]

Project Leader

Viola Vogel


Read more about the Vogel-Group here.