Multi-Scale Model for Melanoma

Current concepts of mechanics in cancer research

Dipl.-ing. Marco Albrecht, PhD student at FSTC Research Group: Systems Biology15.06.2015 Pizza clubmarco.albrecht@uni.lu

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The secret of the difference between in vivo phenomena and experimental 2D cell culture.Holle, Andrew W., Jennifer L. Young, and Joachim P. Spatz. "In vitro cancer cellECM interactions inform in vivo cancer treatment." Advanced drug delivery reviews (2015).2

Some effects3

Tumour mechanicsPressure and stress4

Tumour mechanics5

The role of mechanical forces in tumor growth and therapy (2014) Jain et al.Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors (2012).Stylianopoulos T1, Jain RK

Pressure and stress

The role of mechanical forces in tumor growth and therapy (2014) Jain et al.Cell compression and matrix stiffening Gen expression Proliferation Apoptosis Invasiveness ECMBlood and lymphatic vessel compression. Reduction of oxygen, nutrient and drug delivery Edema

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Pressure and stressSolid stress: Mechanical forces exerted by non-fluid components accumulated within tumours- growth-induced stress remain after resection

- externally applied stress due to surrounding tissueFluid stress: - microvascular pressure (MVP) shear stress- interstitial fluid pressure (IFP)

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Pressure and stress

8Butcher, Darci T., Tamara Alliston, and Valerie M. Weaver. "A tense situation: forcing tumour progression." Nature Reviews Cancer 9.2 (2009): 108-122.

Tumour dynamics

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Tumour dynamics

10Book: Multi scale modelling of cancer (2012) Cristini and Lowengrub

Migration/Invasion

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Cell migration

Tozluolu, Melda, et al. "Matrix geometry determines optimal cancer cell migration strategy and modulates response to interventions." Nature cell biology 15.7 (2013): 751-762.

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Cell migration

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Cell migration

ECM component orientation critical for migration direction

Migration along reassembled collagen fiber highways

Outwardly radiating collagen fiber patterns are observed in vivo and promote invasive behaviour

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Cell mechanics and mechano signal transduction

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Cell mechanics16Youtube: Jochen Guck - Alexander von Humboldt Professorship 2012 (EN)

Otto, Oliver, et al. "Real-time deformability cytometry: on-the-fly cell mechanical phenotyping." Nature methods 12.3 (2015): 199-202.

Guck, Jochen, et al. "Optical deformability as an inherent cell marker for testing malignant transformation and metastatic competence." Biophysical journal (2005)

Cell mechanics

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Dupont, Sirio. "Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction." Experimental cell research (2015).

Mechano signal transduction

18Butcher, Darci T., Tamara Alliston, and Valerie M. Weaver. "A tense situation: forcing tumour progression." Nature Reviews Cancer 9.2 (2009): 108-122.

Traction force microscopyDupont, Sirio. "Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction." Experimental cell research (2015).

Mechano signal transduction

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Humphrey, Jay D., Eric R. Dufresne, and Martin A. Schwartz. "Mechanotransduction and extracellular matrix homeostasis." Nature Reviews Molecular Cell Biology 15.12 (2014): 802-812

Experimental perspective

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Experimental platformsCassereau, Luke, et al. "A 3D tension bioreactor platform to study the interplay between ECM stiffness and tumor phenotype." Journal of biotechnology 193 (2015)21

Experimental platformsStiffness control with natural biomaterials: Collagen gels hyaluronic acid MatrigelBetter stiffness control with artificial biomaterials: Polyacrylamid (PA) Polyethylene glycol (PEG) Polydimethylsiloxane (PDMS)Steering via crosslinker to monomer ratio or photoinitiator systems

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Kloxin, A., Anseth, K. S. (2009). Photodegradable hydrogels for dynamic tuning of physical and chemical properties. Science,

Imaging: Elastography and atomic force microscopy

Kim, Woong, et al. "Application of Elastography for the Noninvasive Assessment of Biomechanics in Engineered Biomaterials and Tissues." Annals of Biomedical Engineering (2016): 1-20.

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Gracias por su atencinmarco.albrecht@uni.lu

Research group Systems Biology at the University of Luxembourg - FSTCKiitos huomiotaGrazie per l'attenzioneEskerrik asko zure arretagatik

Nh s quan tm ca bnObrigado pela sua atenoMerci pour votre attentionDanke fr Ihre Aufmerksamkeitvillmools Merci fir de Opmierksamkeet

Benjamin Ahrenholz24

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The end

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