Pre-doctoral school in QUANTITATIVE BIOLOGY

July 10th- 21st, 2017 | IFOM, Milan - Italy

Multicellular dynamics

Course description

-Second week module-

Collective cell migration refers to the process of many cells migrating as a cohesive group with each individual cell correlating its own movement with that of its neighbors. It is an emergent phenomenon at multicellular level and an inherent part of a developing embryo, a healing wound, a regenerating tissue and a progressing cancer. For example, an increasingly recognized mode of tumor dissemination is through collective migratory/invasive strategies. Under these conditions, tumor cell sheets and strands, or isolated cell cohorts invade the surrounding stroma, gain access to vessels, where collective assemblies of cancerous cells have been shown to resist attrition and to display increased metastatic potential. In this dynamical process, tumor cells interact with the microenvironment and with neighboring tumor cells by exchanging chemical signals and by exerting physical forces. The ability to switch between diverse modes of individual and collective migration enables tumors to adapt to micro-environmental conditions and to metastasize.

One framework to conceptualize the motion of living collective is to equate it to inert particles systems and use basic physical law typically describing soft matter dynamics. For example, recent advances have established that a variety of multicellular entities acquire structural and dynamic physical properties that are surprisingly similar to glassy materials. During collective motility within confluent monolayers cell sheets can flow like a fluid, but as density rises due to proliferation the motion of each cells is constrained by the crowding due to its neighbors, forcing them to move in groups. At a critical density, motility ceases and collectives jam or rigidify undergoing a liquid-to-solid-like transition, surprisingly similar to what is observed in systems of inert particles that undergo a jamming transition at large density. The unjammed-to-jammed transition has been proposed as a general framework to describe collective behavior in cells.

We will reproduce and analyze this transition and explore some of its kinematic features using a simplified in vitro system of cell of epithelial origin, which when seeded in culture dish form monolayers held together by tight cell-cell interactions. As the cells within monolayers divide, they also undergo dramatic kinematic changes before ceasing migration that can be captured through time-lapse microscopy and analyzed using approaches more commonly employed to describe the behavior of inert matter.


Giorgio Scita

IFOM, The FIRC Institute of Molecular Oncology Foundation

Invited Teachers:

Roberto Cerbino holds a PhD in Physics and is currently associate professor of Medical and Applied Physics at the University of Milan. He has been previously a Marie Curie Fellow at the University of Fribourg (Switzerland, 2006) and a visiting researcher at the University of Ottawa (Canada, 2010). His experimental research activity ranges from the study of soft matter (including biological matter) and phase transitions to non-equilibrium statistics and fluid dynamics, with a special attention for the development of innovative optical techniques. Current research topics are: the development of advanced microscopy techniques, scattering and metrology with light and X-rays, arrested dynamics in soft matter systems, instabilities, non-equilibrium fluctuations in complex fluids, motility of cells and other microorganisms.
Fabio Giavazzi holds a Ph.D. in Physics and is currently a Postdoctoral researcher in the Complex Fluids and Molecular Biophysics Lab at the University of Milan. His research activity is focused on development and application of quantitative optical microscopy methods for the investigation of bio-soft matter systems. Recent research topics include: collective motility of cells, dynamics of dense suspensions of motile microorganisms, viscoelasticity and thermal fluctuations in liquid crystals, stress relaxation dynamics in foams and non-equilibrium fluctuations in colloidal systems. He is author of 14 Scopus-indexed publications (Scopus h-index: 6). Fabio Giavazzi is cofounder and former CEO (from 2011 to 2013) of the spin-off company ProXentia, providing commercial analytical devices for rapid testing in the food industry. Past and active industrial collaborations of Fabio Giavazzi (development of advanced optical instrumentation and material testing) include: Solvay, Procter&Gamble , Klinger, Wasatch Microfluidics, ODL. Fabio Giavazzi is inventor of a PCT patented label-free optical method for the detection of molecular interactions.