Projekt

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Novel Microengineered Platform for the Study of Interstitial Cell Migration

Gesuchsteller/in Ferrari Aldo
Nummer 146898
Förderungsinstrument Projektförderung (Abt. I-III)
Forschungseinrichtung Dept. of Mechanical and Process Engineering ETH-Zentrum
Hochschule ETH Zürich - ETHZ
Hauptdisziplin Maschineningenieurwesen
Beginn/Ende 01.09.2013 - 31.07.2017
Bewilligter Betrag 226'603.00
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Alle Disziplinen (2)

Disziplin
Maschineningenieurwesen
Materialwissenschaften

Keywords (4)

Intestitial Cell Migration; Colloidal Self Assembly; Nano Imprint Lithography; Cancer Metastasis

Lay Summary (Italienisch)

Lead
Lo studio della migrazione tumorale è fondamentale per comprendere i processi di evoluzione della malattia e sviluppare strategie terapeutiche per contrastarla. La possibilità di studiare questi processi risulta attualmente limitata dai modelli sperimentali disponibili, che non consentono di controllare le proprietà chimico-fisiche della matrice, e non sono accessibili alla microscopia ad alta risoluzione.
Lay summary

Nuove piattaforme micro-strutturate per lo studio della migrazione interstiziale in cellule

In sintesi

Lo studio della migrazione delle cellule tumorali ha fondamentali risvolti sia nella ricerca dei processi molecolari che portano all’evoluzione della malattia, che nello sviluppo di efficaci strategie terapeutiche per contrastarla. Un aspetto critico nella diffusione delle cellule cancerogene dalla sede primaria ad organi distanti del corpo (il processo di metastasi) riguarda la migrazione all’interno di tessuti connettivi (detta migrazione interstiziale). La possibilità di studiare questi processi risulta attualmente limitata dai modelli sperimentali disponibili, che non consentono di controllare individualmente le proprietà chimico-fisiche della matrice, e non sono accessibili a set-up di microscopia ad alta risoluzione.

Soggetto e obiettivo

Il nostro obiettivo principale è sviluppare una tecnologia in grado di produrre delle piattaforme micro-strutturate che permettano di studiare il processo di migrazione interstiziale di cellule cancerogene. In particolare tali piattaforme consentiranno di i) riprodurre tutti i fondamentali aspetti biologici del processo di migrazione interstiziale, ii) visualizzare il processo di penetrazione interstiziale con microscopia ottica ad alta risoluzione (confocale, total internal reflection, etc.), iii) controllare tutti i parametri chimico-fisici che possono influenzare tale processo, quali la forma, la dimensione, e la rigidità meccanica dei pori.

Contesto socio-scientifico

Il nostro lavoro permetterà di validare un nuovo approccio ingegneristico allo studio dei meccanismi biologici e molecolari alla base della diffusione metastatica delle malattie cancerogene. Il tipo di informazioni scientifiche che deriveranno costituirà una base per lo sviluppo di strumenti diagnostici e per la ricerca di base sulla migrazione tumorale.

Parole chiave

Colloidal Self Assembly, Nano Imprint Lithography, Intestitial Cell Migration, Cancer Metastasis.

Direktlink auf Lay Summary Letzte Aktualisierung: 30.03.2013

Verantw. Gesuchsteller/in und weitere Gesuchstellende

Mitarbeitende

Publikationen

Publikation
A Nanoprinted Model of Interstitial Cancer Migration Reveals a Link between Cell Deformability and Proliferation.
Panagiotakopoulou M Bergert M Taubenberger A Guck J Poulikakos D Ferrari A. (2016), A Nanoprinted Model of Interstitial Cancer Migration Reveals a Link between Cell Deformability and Proliferation., in ACS Nano, 10(7), 6437-6448.

Zusammenarbeit

Gruppe / Person Land
Formen der Zusammenarbeit
Scita Group / IFOM Foundation, Institute FIRC of Molecular Oncology Italien (Europa)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Forschungsinfrastrukturen
Prof. Chew/Howard Hughes Medical Institute, Janelia Advanced Imaging Center Vereinigte Staaten von Amerika (Nordamerika)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Forschungsinfrastrukturen
Kelley Laboratory/University of Toronto Kanada (Nordamerika)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Forschungsinfrastrukturen
- Austausch von Mitarbeitern
Foiani Group/ IFOM Foundation, Institute FIRC of Molecular Oncology Italien (Europa)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten

Wissenschaftliche Veranstaltungen

Aktiver Beitrag

Titel Art des Beitrags Titel des Artikels oder Beitrages Datum Ort Beteiligte Personen
Life Sciences Post Doc Day Vortrag im Rahmen einer Tagung Younger, stronger, more adaptive: the mechanobiology of a post mitotic metastatic cell 09.09.2017 Zurich, Schweiz Panagiotakopoulou Magdalini;
Nanoengineering for Mechanobiology Poster Adaptive Pathfinding in Instertitial Cancer Migration 26.03.2017 Camogli, Italien Poulikakos Dimos; Panagiotakopoulou Magdalini; Ferrari Aldo;
Materials and Processes Graduate Symposium Vortrag im Rahmen einer Tagung Paramorphotic Youth: A 3D Nanoprinted Model Unveils a New Mechanism of Cancer Cell Migration 09.06.2016 Zurich, Schweiz Panagiotakopoulou Magdalini;
Nanoengineering for Mechanobiology Vortrag im Rahmen einer Tagung Cell–cycle dependent cancer migration 03.04.2016 Camogli, Italien Panagiotakopoulou Magdalini; Ferrari Aldo;
ASCB Annual Meeting, 2015 Vortrag im Rahmen einer Tagung Linking nuclear deformability to interstitial migration and proliferation of cancer cells. 12.12.2015 San Diego, Vereinigte Staaten von Amerika Panagiotakopoulou Magdalini;
IFOM-MBI conference Mechanobiology and Cancer Vortrag im Rahmen einer Tagung Interstitial cancer migration through microengineered obstacles 15.07.2014 Milan, Italien Ferrari Aldo; Panagiotakopoulou Magdalini;


Kommunikation mit der Öffentlichkeit

Kommunikation Titel Medien Ort Jahr
Video/Film ACS Nano featured video International 2016
Video/Film Interview at IFOM International 2014

Auszeichnungen

Titel Jahr
ACS Nano cover 2016
Visiting Scientist Grant, Howard Hughes Medical Institute, Janelia Advanced Imaging Center. 2016

Abstract

Cell migration is a multistep process that leads to the translocation of cells across or through a substrate. It is fundamental to cell and tissue dynamics during complex biological activities such as tissue morphogenesis in development and tissue regeneration. Additionally, it contributes to pathological processes such as cancer invasion and metastasis. The basic knowledge on cell migration to date was primarily obtained by studies monitoring the activity of single cells or cell populations contacting two-dimensional (2D) flat surfaces coated with extracellular matrix (ECM) components. This in vitro paradigm offers advantages in terms of accessibility to high-resolution microscopy and allows investigating the migration strategies adopted by cells in specific conditions in vivo such as during epithelial migration in epidermal wound healing. However, during interstitial migration (i.e. the migration of cells through three dimensional - 3D - tissues) activated immune or cancer cells are confronted with a complex microenvironment defined by topographical features of various shape, size and deformability. In this frame, gradients of soluble molecules and the local physical properties of the extracellular environment provide a set of overlapping directional information that cells can read and integrate to follow predisposed patterns, penetrate pores or bypass obstacles on their path. As a consequence, cells modulate their shape, adhesion to the substrate and force generation in migration schemes that are not reproduced by standard 2D models. Interstitial migration is currently investigated using reconstituted 3D matrices or model living tissues. Importantly, these approaches yield a limited accessibility to high-resolution optical techniques and do not allow decoupling the physical parameters involved in the process. The aim of the MicroForm project is the design, fabrication and validation of an original microengineered platform for the study of interstitial cell migration. The platform will be microengineered using a novel on-demand direct printing of colloidal gold nanoparticles self assembled into 3D structures with precisely controlled shapes, sizes and deformability on substrates prepared by lithographic techniques. Additionally, the platform will house a microfluidic device capable of generating spatial and temporal gradients of soluble molecules. The validation and exploitation of the platform will be pursued by high-resolution live-cell microscopy techniques. The platform will feature the following fundamental properties:1.It will provide a controlled and precisely engineered model of the microenvironment encountered by cells during interstitial migration thus recapitulating the basic steps during this activity.2.It will be accessible to standard and advanced microscopy set-ups, including wide-field, confocal and total internal reflection fluorescence (TIRF) microscopy.3.It will allow the independent manipulation of the physical parameters contributing to pathfinding during interstitial migration.Once validated, the platform will be employed to investigate the influence of topography and its interplay with gradients of soluble molecules during interstitial migration. In this activity the platform configuration will be engineered to capture and decouple the role of the shape, size and deformability of interstitial pores and obstacles during cellular pathfinding. In all, the work will significantly add to our fundamental knowledge on interstitial cell migration, as well as develop and test a novel microengineered platform with directly printable non-planar features of further generic utility for such studies.
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